Effect of Mg^(2+)level on the functions of CD8^(+)T lymphocytes and NK cells in patients with COVID-19

Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A total of 165 COVID-19 patients hospitalized in Ezhou Central Hospital from January 20 to February 20,2020 were divided into mild/common group(98 cases)and severe/critical group(67 cases).At the same time,34 healthy persons were selected as the control group.Peripheral blood was collected and PBMCs were isolated,the level of Mg^(2+) in serum and PBMCs was detected.The subsets of CD8^(+)T lymphocytes and NK cell and the expression levels of their surface inhibitory molecular PD-1 and activator molecular NKG2D were detected by flow cytometry.The correlation between Mg^(2+) concentration and the expression levels of PD-1 and NKG2D was also analyzed.Results:Compared with the control group,the concentration of Mg^(2+) in serum and PBMCs,the counts of CD8^(+)T lymphocytes and NK cell in patients with mild/common and severe/critical groups were significantly reduced(P<0.05),while the expression level of surface inhibitory molecular PD-1 were significantly increased(P<0.05),while the expression level of the activation molecule NKG2D were significantly decreased(P<0.05).However,the changes of the above indicators in patients with severe/critical group were greater than those in the mild/common group(P<0.05).In addition,the Mg^(2+) concentration in COVID-19 patients was negatively correlated with the expression level of PD-1 on CD8^(+)T lymphocytes and NK cells(P<0.05),and positively correlated with the expression levels of NKG2D(P<0.05).Conclusion:The concentration of Mg^(2+) in the serum and PBMCs of COVID-19 patients is significantly reduced,which may cause the function of CD8^(+)T lymphocytes and NK cells to be inhibited.

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.

Autoimmune pancreatitis characterized by predominant CD8+ Tlymphocyte infiltration

Autoimmune pancreatitis(AIP)is a rare form of pan-creatitis characterized by prominent lymphocyte inf iltration and pancreatic f ibrosis resulting in organ dysfunc-tion.The pathogenesis and pathology of AIP remain unknown.A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas,elevated IgG levels,and negative autoimmune antibody responses.A pylorus-preserving pancreatoduodenectomy was per-formed and a pancreatic tumor was suspected.Howev-er,periductal lymphoplasmacytic inf iltration and f ibrosis were found in the head of pancreas and nearby organs instead of tumor cells.Four months after surgery,the patient was readmitted because of reoccurrence ofsevere jaundice and sustained abdominal distension.Prednisone 30 mg/d was administered orally as an AIP was suspected.One and a half months later,the symp-toms of the patient disappeared,and globulin,amino-transferase and bilirubin levels decreased signif icantly.Over a 9-mo follow-up period,the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition.We further demonstrated dominant CD3+/CD8+ populations,CD20+ cells and a few CD4+ cells in the pancreatic parenchyma,duo-denum and gallbladder wall by immunohistochemical assay.This AIP case presented with signif icant CD8+ T lymphocyte inf iltration in the pancreas and extra-pan-creatic lesions,indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.

Effects of pituitary adenylate cyclase activating polypeptide on CD4^+/CD8^+T cell levels after traumatic brain injury in a rat model

BACKGROUND： The effect of pituitary adenylate cyclase activating polypeptide （PACAP） during traumatic brain injury （TBI） and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS： Male Sprague Dawley rats were randomly divided into 3 treatment groups （n=6, each）： sham-operated, vehicle （normal saline）＋TBI, and PACAP＋TBI. Normal saline or PACAP （1 μg/5 μL） was administered intracerebroventricularly 20 minutes before TBI. Right parietal cortical contusion was produced via a weight-dropping method. Brains were extracted 24 hours after trauma. Histological changes in brains were examined by HE staining. The numbers of CD4＋ and CD8＋ T cells in blood and the spleen were detected via flow cytometry.RESULTS： In injured brain regions, edema, hemorrhage, inflammatory cell infiltration, and swollen and degenerated neurons were observed under a light microscope, and the neurons were disorderly arrayed in the hippocampi. Compared to the sham group, average CD4＋ CD8＋ lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBl＋vehicle, and CD4- CD8＋ were increased. In rats administered PACAP prior to TBI, damage was attenuated as evidenced by significantly increased CD4＋, and decreased CD8＋, T lymphocytes in blood and the spleen.CONCLUSION： Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.

Role of CD4+ and CD8+ T Lymphocyte in the Onset of Stroke in People Living with HIV in Pointe-Noire

Objective: To determine the role of CD4+ and CD8+ T lymphocytes in the onset of stroke in people living with HIV. Methodology: This was a descriptive, cross-sectional study from January to July 2019, in the neurology department of loandjili general hospital, including any patient hospitalized for a first episode of stroke confirmed by brain scan. The study variables were: age, sex, CRP value, serum T cell CD4+, CD8+. The statistical analysis was carried out using the EPI info 7 software. Results: Twenty stroke patients were included. The relative frequency of HIV was 20%. The risk factors were potentiated by immunosuppression of CD4+ T cells. Sixty percent (60%) of the patients had a CD4+ count < 200/mm3 and the mean CD4+ count was ±191/mm3. Stroke was the predominant mechanism of injury with a frequency of 70%, the only injury mechanism of stroke in patients with CD8+ T cell count > 800/mm3 (p = 0.04). Conclusion: Risk factors are potentiated by TCD4+ lymphocyte immunosupression, also CD8+ lymphocytes of immune system activation marker are a cardiovascular risk factor for living people with HIV.

The difference of immunologic parameters between SARS patients of mild type and severe type

The aim of this study is to study the difference of immunologic parameters between severe acute respiratory syndrome （SARS） patients of mild type and severe type. Data including white blood cell （WBC） count, lymphocyte count, CD3, CD4 and CD8 T lymphocyte count, levels of C3, C4, ESR （erythrocyte sedimentation rate） and CRP （C-reactive protein） from 1291 patients with SARS in each week from onset of illness were recorded. The clinical progress of each sign was analysed and the difference between mild type and severe type was compared. Lymphocyte count, CD8 T lymphocyte count declined in the first two weeks and recovered from the third week, while CRP and CA- levels rose in the first week and then recovered gradually. Lymphocyte count and CD8 T lymphocyte count of severe cases were much lower than that of mild type （P 〈 0.01）, while CRP and CA- levels in severe type were much higher than that of mild type （P 〈 0.01）. Lymphocyte count, CD8 T lymphocyte count, CRP and CA- levels are useful signs for the diagnosis of SARS of severe type and are valuable for the evaluation of its severity.

Role of CD8^(+) T lymphocyte cells:Interplay with stromal cells in tumor microenvironment

CD8^(+) T lymphocytes are pivotal cells in the host response to antitumor immunity.Tumordriven microenvironments provide the conditions necessary for regulating infiltrating CD8^(+) T cells in favor of tumor survival,including weakening CD8^(+) T cell activation,driving tumor cells to impair immune attack,and recruiting other cells to reprogram the immune milieu.Also in tumor microenvironment,stromal cells exert immunosuppressive skills to avoid CD8^(+) T cell cytotoxicity.In this review,we explore the universal function and fate decision of infiltrated CD8^(+) T cells and highlight their antitumor response within various stromal architectures in the process of confronting neoantigen-specific tumor cells.Thus,this review provides a foundation for the development of antitumor therapy based on CD8^(+)T lymphocyte manipulation.

Application of anti-CD103 immunotoxin for saving islet allograft in context of transplantation

Background Previous studies using knockout mice document a key role for the integrin CD103 in promoting organ allograft rejection and graft-versus-host disease. However, a determination of whether blockade of the CD103 pathway represents a viable therapeutic strategy for intervention in these processes has proven problematic due to the lack of reagents that efficiently deplete CD103＋ cells from wild type hosts. To circumvent this problem, in the present study, we invented an anti-CD103 immunotoxin （M290-SAP）. We investigated whether M290-SAP has capacity to eliminate CD103-expressing cells in vivo and protect transplanted islets from destroying by host immune cells.Methods Flow cytometry was used to analyze the efficacy of M290-SAP in depleting CD103-expressing cells in vivo.Then using allogenic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, the therapeutic efficacy of CD103-expressing cell depletion was addressed.Results M290-SAP dramatically reduces the frequency and absolute numbers of CD103-expressing leukocytes in peripheral lymphatic tissues of treated mice. Balb/c islets transplanted into streptozotocin-induced diabetic C57BL/6 mice under single M290-SAP treatment showed an indefinite survival time compared with untreated mice, M290-treated mice and IgG-SAP treated mice （mean survival time, ＞100 days vs. ＜20 days）. C57BL/6 islets transplanted into hyperglycemic NOD mice under single M290-SAP treatment showed a pronounced delay in allograft rejection compared with untreated mice （mean survival time 12-13 days vs. ＜7 days）. Immunological analysis of mice with long-term islet allograft survival revealed an obvious atrophy thymus and severe downregulation of alloimmunity of CD8 subpopulation response to allogenic stimulation.Conclusion Regardless of the underlying mechanisms, these data document that depletion of CD103-expressing cells represents a viable strategy for therapeutic intervention in islet allograft rejection.