Polarization and Apoptosis of T Cell Subsets in Idiopathic Thrombocytopenic Purpura

It is well-known that idiopathic thrombocytopenic purpura （ITP） is an acquired organ-specific autoimmune hemorrhagic disease and dysfunctional cellular immunity is considered important in the pathophysiology of ITP. However, polarization patterns and apoptosis profiles of T lymphocytes remain unclear. In this study, we investigated the polarization of T cell subsets, the expressions of apoptotic proteins Fas/FasL on the subsets and the level of anti-apoptotic gene bcl-2 and bax mRNA. It was demonstrated that the ratios of Thl/Th2 and Tcl/Tc2 in ITP children were increased obviously and that the average percentages were increased clearly for Thl and Th2, but not for Tcl and Tc2. In ITP children, the enhancing expressions were detected for FasL on Thl and Tcl and for Fas on Th2 and Tc2. With increasing level of bcl-2 mRNA and decreasing expression of bax mRNA in ITP children, the ratio of bcl-2/bax mRNA was improved obviously, which was positive correlated with the ratio of Thl/Th2. Taken together, our findings indicate that ITP is a Thl predominant disease. This polarization pattern of T cell subsets might be related to the high ratio of bcl-2/bax mRNA and the abnormal expressions of Fas and FasL on T cell subsets.

The Effect of BCG-PSN on T-cell Subsets and Cytokines in Vernal Conjunctivitis

The effects of BCG PSN on T cell subsets and cytokines in vernal conjunctivitis were observed. The level of total IgE was quantitatively determined before and after treatment with BCG PSN by allergen diagnostic instrument in vitro . The content of T cell subsets of peripheral blood and cytokine were determined by using indirect immune fluorescence method, and IL 4 and INF γ were quantified by ELISA. The results showed that the level of total IgE was substantially reduced ( P <0.01) after treatment in the BCG PSN group. Meanwhile, CD + 8 was decreased, CD + 4 and CD + 4/CD + 8 ratio elevated with significant differences ( P <0.05) as compared with pre treatment results. The changes in total IgE, CD + 8 ,CD + 4 and CD + 4/CD + 8 ratio after treatment also presented significant differences ( P <0.05) between BCG PSN group and routine treatment group. The level of IL 4 in serum declined ( P <0.05) after treatment in the BCG PSN group, and INF γ went up ( P <0 05). IL 4 and INF γ in serum showed significant differences ( P <0.05) between two groups after treatment. It is concluded that BCG PSN has a bi directional immunoregulating effect. It can bring CD + 4 and CD + 8 into homeostasis, thereby preventing the occurrence of anaphylaxis. At the same time, BCG PSN can restrain Th 2, decrease the synthesis of IL 4, switch the balance of Th l/Th 2 to Th 1 side, boost up the predominance of Th 1 relatively, which is propitious to perennial stabilization and recovery of vernal conjunctivitis.

Advanced Glycation End Products Promote Differentiation of CD4^+ T Helper Cells toward Pro-inflammatory Response

This study investigated the effect of advanced glycation end products（AGEs） on differentiation of na ve CD4＋T cells and the role of the receptor of AGEs（RAGE） and peroxisome proliferator-activated receptors（PPARs） activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin（BSA） with glucose. Human na ve CD4＋T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin（sh） RNA knock-down experiment, na ve CD4＋T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-XTM293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4＋T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T（Treg） cells was determined by a [3H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from na ve CD4＋T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in na ve CD4＋T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4＋T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα; PPARγ agonist, PGJ2, inhibited the effect of AGEs on na ve CD4＋T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4＋T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity. ＋

Immunohistochem ical Study of T Lym phocyte Subsets onFrozen Substituted Plastic Em bedding Section of the BoneMarrow from Patients with Myelodysplastic Syndrom e andIts ClinicalIm plication

An immunohistochemical study of T lymphocyte subsets on frozen substituted plastic embedding bone marrow sections obtained from 10 patients with myelodysplastic syndrome (MDS) was presented. The results of qualitative and quantitative immunohistochemical analysis are as follows: (1) Labile antigens of T lymphocytes were well preserved, thus allowing analysis of distribution of T lymphocyte subsets in situ ; (2) the average number of T 3, T 4 and T 8 lymphocyte of the diffuse infiltrate was about 2 %, 0.4 %, 0.5 %, respectively, of all nucleated cells in bone marrow, and T 4/T 8 of T cells were below 1.0 in patients with MDS; (3) there were cases of RAS showing T lymphocyte aggregation in bone marrow, but no patient exhibited progressive refractory anemia with excess of blasts(RAEB) and RAEB in transformation (RAEBT). These findings indicated that the immunological abnormalities are of importance in the evaluation of pathogenesis and prognosis of MDS.

Expression of Snail in bladder urothelial carcinoma and its relationship with E-cadherin and a subset of T cell groups

Objective To investigate the expression of Snail in bladder urothelial carcinoma and evaluate its relationship with E-cadherin and a subset of T cell groups. Methods Immunohistochemical method was used to detect the expression of Snail and E-cadherin proteins in tissue

Parallel decline of CD8+CD38+ lymphocytes and viremia in treated hepatitis B patients

AIM:To assess the peripheral T lymphocyte subsets in chronic hepatitis B virus(HBV) infection,and their dynamics in response to adefovir dipivoxil monotherapy.METHODS:Proportions and absolute counts of peripheral natural killer cells,B cells,CD8+,CD4+,CD8+ CD38+,CD8+CD28+ and CD4+CD28+ T cells were determined using three-color flow cytometry in chronic hepatitis B patients(n = 35),HBV carriers(n = 25) and healthy controls(n = 35).Adefovir dipivoxil was initiated in 17 chronic hepatitis B patients who were regularly followed for 72 wk,during which period the T cell subsets and serum viral load were measured at each follow-up point.RESULTS:The peripheral CD4+ T cell counts and CD8+ T cell counts decreased in chronic HBV infection.In chronic hepatitis B patients,proportions of CD8+CD38+ T cells were 62.0% ± 14.7%,much higher than those of HBV carriers and healthy con-trols.In the 13 hepatitis B patients who were treated and responded to adefovir dipivoxil,proportions of CD8+CD38+ T cells decreased from 53.9% ± 18.4% pre-therapy to 20.1% ± 11.3% by week 72(P < 0.001),concomitant with viral load decline(HBV DNA fell from 7.31 to 3 log copies/mL).CD8+ T cell counts also underwent an average increase of 218 cells/μL by the end of 72-wk treatment.In those who failed the therapy,the CD8+CD38+ T cell population had more fluctuations.CONCLUSION:CD8+ T cells abnormally activated in chronic HBV infection can be partially reversed by antiviral therapy.HBV-associated immune activation may be a crucial part of the pathogenesis and a promising target of treatment.

Immune Function Changes among HIV+/ARC/AIDS Patientsand Its Relationship to Disease Progression

Objective: To analyze HIV replication and immune functionchanges among Chinese patients with HIV/ARC/AIDS andtheir association with disease progression. Methods: T cell subsets, plasma cytokine concentrations andviral loads from 42 HIV+ individuals, and 13 ARC/AIDSpatients, and 10 controls were analyzed by flow cytometry(FCM), quantitative ELISA and reversetranscription-polymerase chain reaction (RT-PCR),respectively. Results: CD4 cell counts and plasma IL-2 in HIV/AIDSpatients were significantly less than in normal control subjects(P<0.001). The plasma concentrations sIL-2R, TNF-α, andNeopterin increased significantly with decreasing CD4 cellcounts. Plasma IL-2 among AIDS/ARC patients was also lessthan in HIV+ patients (P<0.01). CD4 cell counts, the ratio ofCD4 to CD8 and plasma IL-2 levels decreased significantlywith infection duration. CD4 cell counts declined an averageof 43/ml per year. In contrast, the concentration of plasmasIL-2R, sTNFR-I, and Neopterin increased an average of9.03pg/ml, 8.69pg/ml, 2.11ng/ml per yean respectively.Furthermore, a significant reverse linear correlation wasobserved between CD4 cell count, CD4/CD8 ratio, and CD3,CD4 and CD8 counts with plasma levels of sTNFR-I,Neopterin, and HIV RNA load. A positive linear correlationwas noted between plasma sIL-2R levels and changes ofplasma IL-6 level (P<0.001), IL-10(P<0.001), TNF-α(P<0.001),sTNFR-I (P<0.005), and Neopterin (P<0.002) and betweenIL-6 and TNF-α(P<0.001), Neopterin and IL-10 (P<0.05),sTNFR-I (P<0.001), plasma viral load and sTNFR-I (P<0.001),and Neopterin (P<0.002). Conclusion: These findingr suggest a close relationshipbetween IL-6 and TNF-aimmune activation, HIV replicationand disease progression in primary HIV infections and AIDSpatients. Declining CD4 cells and plasma IL-2, and increasingviral load, sIL-2R, TNF-α, sTNFR-I, and Neopterin might beconsidered as important predictors of the progression of HIVinfection to AIDS.

Immune‑Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults

Ageing is often accompanied with a decline in immune system function,resulting in immune ageing.Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence.The change in immune phenotype is a key indication of the diseased or healthy status.However,the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed.Here,we analysed T and natural killer(NK)cell subsets,the phenotype and cell differentiation states in 43,096 healthy individuals,aged 20–88 years,without known diseases.Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals.The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis.Our initial analysis and machine modelling prediction showed that na.ve T cells decreased with ageing,whereas central memory T cells(Tcm)and effector memory T cells(Tem)increased cluster of differentiation(CD)28-associated T cells.This is the largest study to investigate the correlation between age and immune cell function in a Chinese population,and provides insightful differences,suggesting that healthy adults might be considerably influenced by age and sex.The age of a person's immune system might be different from their chronological age.Our immune-ageing modelling study is one of the largest studies to provide insights into‘immune-age’rather than‘biological-age’.Through machine learning,we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction.Our research not only reveals the impact of age on immune parameter differences within the Chinese population,but also provides new insights for monitoring and preventing some diseases in clinical practice.

Relationship between Various Chinese Medicine Types and T-cell Subsets in Patients with Ulcerative Colitis

Objective:To investigate the relationship between various Chinese medicine(CM) types and T-cell subsets(CD4^+ and CD8^+) in the colonic mucous membranes of patients with ulcerative colitis(UC).Methods: Fifty UC patients were enrolled,after differentiation into four types by CM syndromes,i.e.,the internal heat-damp accumulation type(IHDA),the qi-stagnancy with blood stasis type(QSBS),the Pi(脾)-Shen(肾) yang-deficiency type(PSYD) and the yin-blood deficiency type(YBD).From every patient,3-5 pieces of intestina...

3efining the nature of human yo T cells： a biographical ketch of the highly empathetic

The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, 76 T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ap T cells are particularly well equipped to respond to the ＇missing self＇ and the ＇dangerous non-self＇, respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the ＇safe non-self＇ and dealing with the inevitable ＇distressed self＇, and it is within this more complex realm 76 T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human 76 T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life＇s many stresses.

T-bet in the spot light： roles in distinct T-cell fate determination

The transcription factor T-bet was originally described to be important for the differentiation of the CD4＋ Thl subset. More recent investigations implicate T-bet in the lineage commitment of a variety of innate immune cells also. The T-bet appears to have a dual role in the immune system.

Moxibustion versus non-moxibustion for immune reconstitution inflammatory syndrome in patients with HIV:A 48-week prospective cohort study

Objective:To assess the effects of moxibustion on immune reconstitution inflammatory syndrome(IRIS)in patients with acquired immune deficiency syndrome(AIDS)by tracking T-cell subsets over a 48-week prospective cohort study.Methods:Patients with AIDS who had low viral loads and weakened immune systems were divided into a moxibustion group and a non-moxibustion group.The non-moxibustion group received standard western treatment,including 48 weeks of antiretroviral therapy(ART).The moxibustion group received ART combined with moxibusion therapy,administered three times weekly.Each treatment lasted 10 weeks,with four courses completed over 48 weeks,separated by 2-week breaks.At different time points,plasma levels of CD4^(+),CD8^(+),CD45RAt,CD45RO^(+),CD4^(+)CD28^(+),CD8^(+)CD38^(+),and CD4^(+)CD38^(+)were compared between the two groups.Results:A total of 200 eligible patients were included and divided into two groups,with 100 in the non-moxibustion group and 100 in the moxibustion group.At Week 24,the CD4^(+)T cell count was(180.71±79.62)cells/μL in the non-moxibustion group and(218.22±82.02)cells/μL in the moxibustion group.By Week 36,the counts were(204.83±96.78)cells/μuL and(239.35±81.90)cells/μL,respectively.At Weeks 24 and 48,the CD8^(+)T cell and CD45RO^(+)counts were higher in the moxibustion group than in the non-moxibustion group(P<0.05).By Week 48,the CD45RA^(+)count was also higher in the moxibustion group(P<0.05).At Week 24,the CD4^(+)CD25^(+)count was lower in the moxibustion group than in the non-moxibustion group(P<0.05).