Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.

Impact of nanoparticles on immune cells and their potential applications in cancer immunotherapy

Nanoparticles represent a heterogeneous collection of materials,whether natural or synthetic,with dimensions aligning in the nanoscale.Because of their intense manifestation with the immune system,they can be harvested for numerous bio-medical and biotechnological advancements mainly in cancer treatment.This review article aims to scrutinize various types of nanoparticles that interact differently with immune cells like macrophages,dendritic cells,T lymphocytes,and natural killer(NK)cells.It also underscores the importance of knowing how nanoparticles influence immune cell functions,such as the production of cytokines and the presentation of antigens which are crucial for effective cancer immunotherapy.Hence overviews of bio-molecular mechanisms are provided.Nanoparticles can improve antigen presentation,boost T-cell responses,and overcome the immunosuppressive tumor environment.The regulatory mechanisms,signaling pathways,and nanoparticle characteristics are also presented for a comprehensive understanding.We review the nanotechnology platform options and challenges in nanoparticlesbased immunotherapy,from an immunotherapy perspective including precise targeting,immune modulation,and potential toxicity,as well as personalized approaches based on individual patient and tumor characteristics.The development of emerging multifunctional nanoparticles and theranostic nanoparticles will provide new solutions for the precision and efficiency of cancer therapies in next-generation practice.

T lymphocyte proportion in Alzheimer’s disease prognosis

Bai et al investigate the predictive value of T lymphocyte proportion in Alzheimer's disease(AD)prognosis.Through a retrospective study involving 62 AD patients,they found that a decrease in T lymphocyte proportion correlated with a poorer prognosis,as indicated by higher modified Rankin scale scores.While the study highlights the potential of T lymphocyte proportion as a prognostic marker,it suggests the need for larger,multicenter studies to enhance generalizability and validity.Additionally,future research could use cognitive exams when evaluating prognosis and delve into immune mechanisms underlying AD progression.Despite limitations inherent in retrospective designs,Bai et al's work contributes to understanding the immune system's role in AD prognosis,paving the way for further exploration in this under-researched area.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

Predictors of prognosis in Alzheimer’s disease: The role of cognitive dysfunction, immune abnormalities, and advanced neuroimaging

Alzheimer’s disease(AD)is a grave illness that results in cognitive and social issues.A recent study examined the association between neuroimaging results,cognitive dysfunction,atypical cellular immune function,and poor prognostic factors in AD patients who demonstrated poor prognosis.Poor prognosis was associated with abnormal cellular immune function,extrapyramidal symptoms,altered consciousness,abnormal electroencephalogram,modified Rankin scale,increased neutrophil lymphocyte ratio,and severe pneumonia.The impaired cellular immune function characterized by a reduction in the blood T lym-phocytes’proportion predicted poor prognosis as an independent risk factor in AD.Early initiation and maintenance of AD medications is associated with better outcomes.

Clinical evaluation of sintilimab in conjunction with bevacizumab for advanced colorectal cancer with microsatellite stable-type after failure of first-line therapy

BACKGROUND At present,immune checkpoint inhibitors(ICIs)remain the 1st-line therapy me-thod for patients suffering from high microsatellite instability/deficient misma-tch repair metastatic colorectal cancer(mCRC).However,ICI treatments demon-strate minimal therapeutic efficacy against microsatellite stable(MSS)/proficient mismatch repair(pMMR)CRC.This is mainly because this type of tumor is a“cold tumor”with almost no lymphocyte infiltration.Anti-angiogenic drugs have been found to improve the immune microenvironment by promoting many immune cells to enter the immune microenvironment,thereby exerting anti-tumor effects.AIM To investigate the effects of ICIs combined with bevacizumab monoclonal anti-body on tumor immune cells in MSS/pMMR advanced CRC patients with first-line treatment failure.METHODS A total of 110 MSS/pMMR patients with advanced CRC after first-line treatment failure in the Affiliated Hospital of Qinghai University were enrolled for a ran-domized controlled trial.In short,patients in the experimental group(n=60)were given sintilimab plus bevacizumab for 4 cycles,and those in the control group(n=50)patients were treated with FOLFIRI combined with bevacizumab for 4 cycles.The expression levels of cluster of differentiation(CD)8(+)T cells,tumor-associated macrophages(TAMs),and cancer-associated fibroblasts(CAFs)were comprehensively evaluated to assess the effects of sintilimab combined with bevacizumab on MSS/pMMR advanced CRC sufferers following failure of 1st-line therapy.RESULTS The positive expression rates of CD8(+)T lymphocytes(30%vs 50%),TAMs(23.30%vs 60%),and CAFs(23.30%vs 50%)before and after treatment in both groups exhibited statistical significance(P<0.05).Additionally,the therapeutic effects of both groups(partial remission:26.67%vs 10%;objective response rate:26.70%vs 10%)were significantly different(P<0.05).Although the experimental group showed a higher progression-free survival,median progression-free survival,and disease control rate than the control group,the difference was not statist-ically significant.Moreover,no significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups was found(P>0.05).CONCLUSION ICIs in combination with bevacizumab can not only improve the patient’s prognosis but also yield safe and controllable adverse drug reactions in patients suffering from MSS/pMMR advanced CRC after failure to a 1st-line therapy.

Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma

Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.

Subgroups of peripheral immune effector cells in cervical cancer patients are more sensitive to radiation therapy than chemotherapy

Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.

Correlation Study Between T Lymphocyte Subsets and Rheumatoid Arthritis

Objective:To study the effect of Helicobacter pylori infection on rheumatoid arthritis and T-lymphocyte subpopulations in patients with rheumatoid arthritis and to provide a new method for the treatment of rheumatoid arthritis by removing Helicobacter pylori from patients.Methods:60 patients with rheumatoid arthritis admitted to the hospital from May 2022 to May 2023 were selected for the study,and all patients underwent a 13-carbon urea breath test to detect gastric H.pylori and the test results showed that 20 cases were negative and 40 cases were positive.The 40 positive patients were divided into the treatment group(n=20)and non-treatment group(n=20)by random number table method and the treatment group was given anti-Helicobacter pylori treatment,and the non-treatment group was given maintenance rheumatoid basic treatment,comparing the anti-cyclic citrulline peptide(CCP),DS28 score,peripheral blood T-lymphocyte subsets(CD4^(+)T-lymphocytes,CD8^(+)T-lymphocytes,CD4^(+)/CD8^(+)ratio)before and after the treatment of patients by 13-carbon urea respiration test(pylori-negative group,20 patients)and those who were positive for the treatment of H pylori(pylori-positive group,40 patients).Besides,the correlation of peripheral blood T-lymphocyte subsets and disease activity between treatment and non-treatment groups in the pylori-positive group was identified together with the correlation of DS28 scores,TNF-αlevels,sedimentation and immunoglobulin,lymphocyte subsets in the pylori-positive treatment group and positive non-treatment group as well as the level of globulin,lymphocyte subsets,and peripheral blood lymphocytes before and after treatment.Results:Before treatment,CCP,DS28 score,CD8^(+)T lymphocyte level of the pylori-negative group were lower than that of the positive group,and CD4^(+)T lymphocyte and CD4^(+)/CD8^(+)ratio were higher than that of the positive group(P<0.05);after treatment,the indexes of the pylori-positive group improved,and there was no significant difference in the comparison of the indexes with those of the pylori-negative group(P>0.05);the positive treatment group had a DS28(3.19±1.02)points,positive non-treatment group DS28(5.36±1.85)points,non-treatment group DS28 score and CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)negative correlation with CD8^(+)T lymphocytes showed a positive correlation(P<0.05);before the treatment,pylori-positive treatment group and non-treatment group DS28 scores,TNF-αlevels,peripheral blood T lymphocyte subpopulation levels were not significantly different(P>0.05);after treatment,DS28 score,TNF-αlevel,CD8^(+)T of the treatment group were lower than those of the non-treatment group,and CD4^(+)T lymphocytes and CD4^(+)/CD8^(+)ratio were higher than those of the non-treatment group(P<0.05).Conclusion:H.pylori affects the level of T lymphocyte subsets in patients with rheumatoid arthritis,and there is a certain correlation between the two.Removal of H.pylori can improve the level of T lymphocyte subsets,which is important for the treatment of patients with rheumatoid arthritis.

Bystanders or not?Microglia and lymphocytes in aging and stroke

As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’T cell ferroptosis

BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.

Association of T lymphocyte subset counts with the clinical features of colorectal cancer

Background:Colorectal cancer(CRC)is a common gastrointestinal malignancy.The T lymphocyte subsets are important in the develop-ment,invasion and metastasis of tumors,including CRC.Nevertheless,limited research has explored the relationship between T cell subpopu-lations and the clinical characteristics of CRC.This study compared the T lymphocyte subsets in patients with CRC and healthy individuals,and assessed the relationship between these values and clinical characteristics.Methods:Peripheral blood was collected from 100 patients with CRC and 54 healthy individuals.The numbers of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes,NK cells,and the CD4^(+)T/CD8^(+)T ratio in peripheral blood were measured using flow cytometry,and were compared between CRC patients and healthy individuals.Spearman's correlation analysis was performed to investigate the relationship between the T lymphocyte subsets in patients diagnosed with CRC and the levels of carcinoembryonic antigen(CEA)and thymidine kinase 1(TK1).Receiver operating characteristic(ROC)curves were utilized to evaluate the potential utility of the T lymphocyte counts in predicting lymph node metastasis,vas-cular infiltration,and high Ki-67 expression.Results:The CRC patients had lower counts of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes compared to the healthy population(P<0.05).However,no significant differences were observed in the CD4^(+)/CD8^(+)ratio or NK cells(P>0.05).Notably,the CD3^(+)T,CD4^(+)T,and CD8^(+)T lym-phocyte counts were higher in patients with stageⅠ-Ⅱdisease,no lymph node metastasis,no vascular invasion,and low Ki-67 expression than in those with stageⅢ,lymph node metastasis,vascular invasion,and high Ki-67 expression(P<0.05).There was a negative association be-tween the CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts and CEA and TK1 levels in patients with CRC.The ROC curves demonstrated that CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts had significant predictive value for lymph node metastasis,vascular infiltration,and high Ki-67 expression.Conclusions:The peripheral blood CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts are related to the clinical traits of patients with CRC and can predict the prognosis of the disease.

Haematology Parameters of Apparently Healthy Prospective Whole Blood Donors in a Nigerian Hospital Setting

Background: Adequate selection of a prospective whole blood donor protects his health and safety of the recipient. Objectives: The main objective of this study was to determine the haematology parameters of apparently healthy prospective whole blood donors. Participants and Methods: This was a hospital based prospective study carried out from August to October 2020 at the blood transfusion unit of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria. A structured pretested questionnaire was used for data collection. The socio demographic status and the haematology parameters of apparently healthy prospective whole blood donors who tested negative for HIV, hepatitis B and C markers were captured. Obtained data were analysed with the statistical package for the social scientist software version 20. Results: One hundred male (97.1%) and three female (2.9%) apparently healthy prospective whole blood donors were studied. The median age of study subjects was 30 years. Obtained median haematology parameter values were 13 g/dl, 40%, 4.9/nl and 203.9/nl for haemoglobin concentration, haematocrit, total white cell and platelet counts respectively. The median values for the mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) of participants were 32.6 g/dl, 27.7 pg and 85.7 fl respectively. Observed prevalence of subnormal haematology parameters for haemoglobin concentration, total white cells, platelets were 12.6%, 25.2%, and 13.6% respectively. Also subnormal values for MCHC, MCH, MCV were 11.7%, 26.2%, and 16.5% respectively among prospective whole blood donors in this study. No higher than normal haematology parameter values were observed. Median values for erythrocyte sedimentation rate was 8.4 mm/hr. Conclusion: A significant percentage of apparently healthy prospective whole blood donors had subnormal haematology parameters values. Obtained normal values in our study are comparable with local reference range reports from previous studies in Nigeria and other parts of Africa. 124947 .

Effects of Three Kinds of Chinese Medicine Polysaccharides on the Immune Effect of Newcastle Disease Vaccine

240 14-day-old healthy and non-immune Roman chicken were randomly divided into 8 groups, including blank control group （BC group）, immune control group （IC group）, and immunity groups of each Chinese medicine. On the day of the first immunity, 3 d before the second immunity, the day of the second immunity and 3 d after the second immunity, high-dose concentration and low-dose concen- tration of Astragalus polysaccharide （ASP）, Epimedium polysaccharide （EPP） and Isatis roots polysaccharide （IRPS） were used for the immunity groups of each Chi- nese medicine using the gavage, and 0.5 ml for each chick, and the equivalent normal saline was used for the blank control group and vaccine control group. On the 7^th, 14^th, 21^st and 28^th day after the first immunity, 10 chicken of each group were randomly got and weighed, and the antibody titer and the changes of the pro- liferation of T lymphocyte were measured. The results showed that 3 kinds of Chi- nese medicine polysaccharides all can increase the weight of chicken, improve HI antibody titer of Newcastle disease, and promote the proliferation of peripheral T lymphocyte, in which the effect of IRPS at low dosage is the best.

Fixed-Tumor Vaccine: A Practical Formulation with Cytokine-Microspheres for Protective and Therapeutic Antitumor Immunity

Objective: To study the protective and therapeutic antitumor immunity against hepatocellular carcinoma (HCC) with the fixed-tumor vaccine.Methods: A tumor vaccine consisting of fixed tumor cells or fixed tumor fragments combined with sustained-releasers of cytokines and a non-toxic adjuvant was developed. C57BL/6J mice were immunized intra-dermally with the vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa 1–6 cells.Results: All of 15 nonimmunized control mice developed the hepatoma. Protection of mice immunized with fixed Hepa 1–6 cells and both of IL-2/GM-CSF microspheres or further mixed with TiterMax Gold reached 80% and 87%, respectively. Mass growth of the established tumors, vaccinated twice at 5 mm in diameter, the tumor of control animals continued to grow. However, 7–10 days after the second injection of the tumor vaccine, the tumor growth was suppressed in 9 of 10 mice and then markedly reduced. Complete tumor regression was observed in 60% (6/10) of mice. Splenocytes from the control mice were not able to lyse target Hepa 1–6 cells and other tumor cells. In contrast splenocytes from the vaccinated mice exhibited a 41% lytic activity against the Hepa 1–6 cells tested at an effector/target (E/T) ratio of 5, whereas they did not exhibited such activity against the melanoma cells (B16-F1), Lewis lung carcinoma cells (LLC), renal carcinoma cells (Renca), and bladder carcinoma cells (MBT-2). The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class I monoclonal antibodies but not with anti-CD4 and anti-MHC-class II antibodies. In the Phase-I clinical trial, vaccination of HCC patients with the autologous vaccine is a well-tolerated treatment and induces fixed tumor fragment-specific immunity.Conclusion: Fixed HCC vaccination elicited protective and therapeutic antitumor immunity against HCC. The tumor vaccine elicited antigen specific CTL response lysis of the target HCC was mediated by the typical MHC-class I restricted CD8+ T cells. Key words cancer vaccine - cytotoxic T lymphocyte - immunotherapy - hepatoma

Experimental Study on Double Blocking of T Lymphocytes Apoptosis Induced by Fas/FasL

Objective： To block the apoptosis of T lymphocytes induced by Fas/FasL in order to establish a method of the large-scale preparation of large amounts of tumor-specific cytoxic T-lymphocytes （CTL）. Methods： Liver cancer cells and tumor infiltrating lymphocytes （TIL） were isolated from FasL positive fresh specimens, and co-cultured. Specific CTL were activated and prepared in the presence of the co-stimulation of monoclonal antibody CD28. Then the blocking and activation of apoptosis of T lymphocytes was activated by soluble Fas receptor, which was detected by cytometry and DNA ladder test simultaneously. The apoptosis-blocking effect was compared with the control group. Furthermore, the changes of T cell proliferation and killing activity were detected by the method of ^3H thymidine incorporation and ^51Cr release test. Results： There was a significant increase in apoptosis rate in unblocking group compared with blocking group and quiescent group, with the unblocking group of 47.82%±0.13%, quiescent group of 3.76%±0.25%, and the blocking group of 8.22%±0.26% respectively （P〈0.01）. T cell-ladder appeared in unblocking group by DNA ladder test. Both the killing ability and proliferation rate of T cells were significantly increased after blocking. There was significant difference among blocking group, unblocking group and quiescent group （P〈0.01）. Conclusion： With this method we obtained large amounts of tumor-specific T lymphocytes, which was able to kill liver cancer cells effectively.

Immunopotentiating Effects of Cucurbitacin B in Mice

Cucurbitacin B(CUB)is a major active principle contained in the calyx melo of Cucumis melo L.The immunopotentiating effects of CuB(im,qd×5)were studied.At lower doses, CuB increased the number of peripheral blood T lymphocytes(0.1 mg/kg),the rate of PHA-induced lymphocyte transformation(0.2 mg/kg),the number of plaque forming cells(PFC)of the spleen(0.2 mg/kg)and the level of serum hemolysin(0.4 mg/kg).The phagocytosis of macrophages and the clearance rate of charcoal particles were enhanced only by a large dose(0.8 mg/kg).The results indicate that CuB can potentiate both cellular and humoral immune function.

Fas and Bc1-2 EXpression on T Lymphocyte Subsets in the Peripheral Blood of Relapsing Patients with Condyloma Acuminatum

Objective: To study the expression of Fas and Bcl-2proteins on T lymphocyte subsets in the peripheralblood of relapsing patients with condyloma acuminatum(CA) and healthy controls. Methods: Flow cytometry (permeabization andstaining procedure with conjugated antibodies) wasused. Results: We observed that the expression of Fasprotein on CD4^+ T lymphocyte subset of CA patientswas significantly higher than that of healthy controls(P<0.01). Conclusions: Increased expression of Fas proteinon CD4^+ T lymphocyte subset may be a cause of de-creased percentage of CD4^+ T lymphocyte subset. Thisinduces the increased ratio of CD4^+/CD8^+.

Intracellular Cytokine Expression Profile in Patients with Condyloma Acuminata

Objective: To study the immunological mechanisms ofCondyloma acuminata(CA) through investigating Tlymphocyte subset levels and cytokine profile in theperipheral blood of patients with CondylomaAcuminata. Methods: Tricolor and bicolor immunofluorescentstaining antibody of cell surface antigen and intracel-lular IL-2, IL-4, IL-12, IFN-Y in CD4^+ and CD8^+ T-lymphocytes from 20 patients with CA were performedand followed by flow cytometry. Results: The number of CD3^+T, CD4^+T-lymphocytescells and CD4^+/CD8^+T cells ratio were significantlydecreased(P<0.01) in patients with CA Compared tocontrols, and IL-2, IL-12, IFN-γ production in CD4^+Tcells was decreased(P<0.01), IL-4 and IFN-γ produc-tion in CD4^+T cells was not significantly different (P>0.05), while IL-2 and IL-12 production in CD8^+Tc cellswas decreased (P<0.01), whereas IFN-γ and IL-4 pro-ducing in CD4^+T cells were of no significantlydifference(P>0.05). Conclusions: There was an imbalance of T lympho-cyte subsets, Th1/Th2 cytokines and Tc1/Tc2 in theperipheral blood of CA patients, which may play animportant role in the pathogenesis and progression ofCA.

Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

AIM： To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus （HBV） replication in different dinical stages of chronic HBV infection. METHODS： A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages： immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time poiymerase chain reaction.RESULTS： CD8^＋ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages （36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P 〈 0.001）. The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8^＋ T-cells than CD4^＋ T-cells （36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P 〈 0.01）, whereas the peripheral blood in patients at the immune- inactive carrier stage and in normal controls contained less CD8^＋ T-cells than CD4^＋ T-cells （28.09 ± 5.64 vs 36.85 ±6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P 〈 0.01）. ANOVA linear trend test showed that CD8^＋ T-cells were significantly increased in patients with a high viral load （39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P 〈 0.001）, while CD4^＋ T-cells were significantly increased in patients with a low HBV DNA load （37.45 ± 6.24, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P 〈 0.001）. Nultiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3^＋, CD4^＋ and CD8^＋ cells and CD4^＋/CD8^＋ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.CONCLUSION： Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.