CD28-T细胞亚群在类风湿关节炎患者外周血和关节液中的表达

目的 探讨CD28-T细胞亚群在类风湿关节炎(RA)患者外周血和关节液中的变化和意义。方法 随机选择RA患者45例,取新鲜抗凝外周血单个核细胞(PBMC),其中15例同时提取关节液单个核细胞( SFMC),以流式细胞技术检测CD28-T细胞数量及其表面可诱导共刺激分子(ICOS)的表达。2 组间比较用独立样本t检验。结果 ①与PBMC相比,RA患者SFMC中CD4+CD28+ ICOS+、CD4+CD28-ICOS+、CD8+ CD28+、CD8+ CD28+ ICOS+T细胞明显升高[(36±19)％与(15±8)％,t=-4.234,P＜0.01;(2.1±2.2)％与(0.6±1.4)％,t=-3.143,P＜0.01;(62±15)％与(47±18)％,t=-2.885,P＜0.01;(9±9)％与(3±3)％,t=-2.131,P＜0.05];CD8+CD28-T细胞明显降低[(38±15)％与(54±18)％,t=2.975,P＜0.01];CD8+ CD28- ICOS+、C1D4+CD28+和CD4+CD28-T细胞无明显变化（P＞0.05）。②同一RA患者SFMC与PBMC相比,CD4+CD28+ICOS+、CD8+ CD28+T细胞明显升高[(38±18)％与(16±10)％,t=-4.065,P＜0.01;(61±16)％与(41±21)％,t=-2.883,P＜0.01];CD8+ CD28-T细胞明显降低[(39±16)％与(59±21)％,t=2.949,P＜0.01]。③缓解期与活动期RA患者相比,PBMC中CD4+CD28-、CD8+ CD28-、CD28-ICOS+T细胞无明显变化（P＞0.05）。结论 RA患者关节液中CD28-T细胞亚群失衡和ICOS分子表达异常,可能是导致RA关节损伤的重要机制。     

淋巴细胞激活诱导的受体4-1BB在类风湿关节炎T淋巴细胞亚群上的表达

目的探讨类风湿关节炎(RA)T淋巴细胞上淋巴细胞激活诱导的受体4-1BB的表达及其作用机制。方法应用流式细胞术检测30例RA患者和20名正常对照者外周血T细胞活化前后4-1BB的表达。结果RA患者CD4~ T和CD8~ T细胞表达的4-1BB明显高于正常对照组[表达百分率分别为(18．56±4．08)％,(10．33±2．13)％,(1．24±0．12)％,(0．87±0．09)％,P＜0．01],经抗CD3单抗体外刺激后CD4~ T和CD8~ T细胞表达的4-1BB均显著高于活化前[表达百分率为(33±4)％和(21±8)％,P＜0．01]。RA患者CD4~ T/CD8~ T比值明显升高,而且与4-1BB~ CD4~ T细胞数呈正相关关系(r=0．84,P＜0.01),另外4-1BB~ CD4~ T细胞数与血沉、IgA呈正相关关系(r=0．476,P＜0．05；r=0．659,P＜0．05)。结论RA患者T细胞表达的4-IBB在RA的发生发展中具有重要意义,4-1BB可能通过对CD4~ T活化与增殖参与关节炎症和免疫反应。     

单核细胞趋化蛋白在强直性脊性炎患者中的表达与意义

目的 旨在通过检测强直性脊性炎(AS)病人的外周血单个核细胞(PBMC)、关节滑液单个核细胞(SFMC)和滑膜细胞中趋化因子单核细胞趋化蛋白(MCP)基因表达水平，了解它们在AS中的变化及其在关节炎发病机制中的作用和意义。方法 选取健康志愿者和AS病人的PBMC基因表达谱，通过含1176基因的cDNA微阵列扫描结果得到，筛选出的差异表达基因再以反转录-聚合酶链反应(RT-PCR)方法验证AS病人PBMC、SFMC和AS患者滑膜中的表达水平。结果 MCP-1在AS患者SFMC表达明显高于健康志愿者的PBMC和AS病人的PBMC。AS患者SFMC中的MCP-1水平与MCP-3水平呈正相关(r=0．76，P=0．003)；MCP-1在AS患者的关节滑膜细胞的表达水平明显高于健康对照者的关节滑膜细胞(P=0．0035)；脂多糖(LPS)刺激4h后，AS患者和健康志愿者的外周血单核细胞的MCP-1的表达显著增高。结论 MCP—1在AS病人SFMC和关节滑膜细胞中呈高表达，提示MCP-1可能在AS病人的炎症细胞向关节的归巢以及关节局部的炎症反应中起重要作用。     

类风湿关节炎患者Th1/Th2细胞平衡的研究

目的　在单个细胞水平上研究类风湿关节炎 (RA)患者滑液及外周血中Th1/Th2细胞平衡状态及其与疾病活动程度的关系。方法　用酶联免疫斑点法 (ELISPOT)检测RA患者滑液单个核细胞 (SFMC)和外周血单个核细胞 (PBMC)的细胞内细胞因子IFN γ和IL 4的表达情况。结果　RA患者SFMC中Th1及Th1/Th2比值与自身及正常人PBMC相比显著升高 (P <0 0 1) ,Th1/Th2比值与患者Stoke指数呈正相关 (r =0 893,P <0 0 1)。结论　在RA患者关节中细胞因子分泌模式朝Th1偏移 ,Th1/Th2比值与疾病活动性相关 ,Th1/Th2平衡在RA发病机制及疾病进展中起重要作用。     

类风湿关节炎患者外周血CD4 T细胞关节局部趋化机制

目的探讨类风湿关节炎(RA)患者外周血CD4 T细胞比例变化情况及其对关节局部趋化的机制。方法流式细胞术分析RA患者外周血单个核细胞(PBMC)中CD4 T细胞的比例,并分析CD4 T细胞比例与RA疾病活动性评分系统(DAS28)评分间的关系。激光共聚焦方法检测RA患者滑膜局部浸润CD4 T细胞情况。流式细胞术分析RA患者CD4 T细胞表面趋化因子受体表达情况。结果与对照组相比,RA患者外周血PBMC中CD4 T细胞的比例显著降低(P0.01),且RA患者外周血CD4 T细胞比例与DAS28评分呈明显负相关(r=-0.753 0,P=0.001 2)。关节局部CD4 T细胞浸润的激光共聚焦结果显示,与对照组相比,RA患者滑膜中具有更多的CD4 T细胞浸润。趋化因子受体分析结果显示,RA患者外周血CD4 T细胞表面CCR5、CXCR1和CXCR3的表达显著升高(P0.01)。结论 RA患者外周血CD4 T细胞表面表达升高的CCR5、CXCR1和CXCR3可能参与外周血CD4 T细胞向滑膜局部的趋化。     

脊柱关节病患者外周血和关节液单个核细胞基因谱的研究

目的：了解脊柱关节病（SpA）患者外周血和关节液单个核细胞（SFMC）基因的变化及其特点，探讨与SpA关节炎相关的基因及可能的意义。方法：采用含1176个基因的cDNA微阵列，检测6名健康志愿者外周血单个核细胞（PBMC），5例SpA和5例类风湿关节炎（RA）病人PBMC和关节液SFMC的基因表达，挑选SpA SFMC表达异常的9个致炎、抗炎、信号传导基因或受体和粘附分子，扩大病例数以半定量PCR再验证微阵列检测结果。结果：cDNA微阵列和PCR结果显示，1176cDNA微阵列基因图谱和阳性基因数量在RA和SpA病人SFMC组无明显区别，比较SpA或RA病人的SFMC和PBMC，发现SpA和RA的SFMC中的阳性基因均少于各自的PBMC。在RA的PBMC有53个基因明显高于RA SFM（P＜0．05），但在SpA PBMC仅有5个基因明显高于SpA SFMC(P＜0．05）。SpA病人SFMC的IL－1β、TNF-α、TGF-β、TGF-β2、c-jun、JAK-显著高于健康人PBMC（P＜0．05）。结论：SpA患者的SFMC基因表达谱异常，但与RA的SFM未见明显特征型区别，IL－1β、TNF-α、TGF-β、TGF-β2、c-jun、JAK-3与SpA关节炎的发生和发展相关。     

正性共刺激分子ICOS/ICOSL、OX40/OX40L对老年2型糖尿病免疫炎症的调节作用

目的探讨正性共刺激分子ICOS/ICOSL、OX40/OX40L对老年2型糖尿病免疫炎症的调节作用及临床意义。方法老年2型糖尿病患者40例作为研究组,另随机选取同期接受体检的健康老年人40例作为对照组,均展开共刺激分子ICOS/ICOSL、OX40/OX40L检测,对比分析两组检测结果。结果研究组B细胞、CD4~+T细胞上的ICOS/ICOSL、OX40/OX40L表达水平显著高于对照组(P0.05);合并大血管病变的患者B细胞、CD4~+T细胞上ICOS/ICOSL、OX40/OX40L表达均显著高于未合并者(P0.05);研究组ICOS/ICOSL与dsDNA抗体、IgG抗体呈正相关,OX40/OX40与抗核抗体水平呈正相关。结论正性共刺激分子ICOS/ICOSL、OX40/OX40L参与老年2型糖尿病的免疫炎症调节,对其实施检测有望提供老年2型糖尿病诊治与并发症预防的新思路。     

老年高血压患者外周血T淋巴细胞表面抗原表达的研究

目的:探讨老年人外周血T淋巴细胞表面抗原CD45RA和CD45RO的表达及其与高血压的关系。方法:收集44例60岁以上老年人外周静脉血,按高血压诊断标准分为老年对照组(25例)和老年高血压组(19例),另收集20例健康成年人外周静脉血(成年对照组),均分离外周血单个核细胞,通过流式细胞仪检测CD45RA+和CD45RO+占CD4+T淋巴细胞的百分比,分析CD45RA和CD45RO抗原表达的相对关系。结果:老年对照组外周血CD45RA+占CD4+T淋巴细胞的百分比较成年对照组显著降低,CD45RO+占CD4+T淋巴细胞的百分比较成年对照组显著升高(均P0.05);与老年对照组相比,老年高血压组外周血CD45RO+占CD4+T淋巴细胞的百分比显著升高,45RA+/CD45RO+的比值显著降低(均P0.05)。结论:T淋巴细胞表面抗原CD45的表达变化提示T淋巴细胞的过度激活分化,可能参与了老年高血压的发病。     

CXCR3 CCR5及其配体在类风湿关节炎患者滑液和外周血中的表达

目的 在单细胞水平上，研究类风湿关节炎（RA）患者滑液及外周血中单核/巨噬细胞，T淋巴细胞上趋化因子受体CCR5及ＣＸＣＲ３的表达。并测定CCR5的配体MIP-1β。激活正常T细胞表达和分泌因子（RANTES）及T细胞亚群，探讨其在RA发病中的作用机制。方法 分离RA患者滑液单个核细胞（SFMC），外周血单个核细胞（PBMC）及正常人PBMC（对照），以三色荧光素标记物进行流式细胞术分析CD14^ ,CD3^ 细胞膜表面趋化因子受体CCR5，CCR3及细胞内趋化因子MIP-1β，RANTES和细胞因子白细胞介素（IL）-4，干扰素（IFN）-γ的表达率。结果 与PBMC相比，RA患者SFMC中的单核/巨噬细胞，T细胞上趋化因子受体CCR4及CEXR3表达显著增高；且单核/巨噬细胞分泌趋化因子MIP-1β，RANTES的百分比较高；SFMC中Th1细胞亚群（即IFN-γ^ T细胞）的表达率与滑液及外周血中T淋巴细胞上趋化因子受体CCR4及CXCR3的表达率显著相关。结论 趋化因子受体CCR5^ ,CXCR3^ 的单核/巨噬细胞，T细胞积聚在RA患者的病变关节内，且单核/巨噬细胞分泌较多趋化因子；CCR5，CXCR3可能参与调节细胞移动。与Th1细胞亚群及其“伙伴”细胞在RA关节内积聚有关；可能与RA的发病相关。     

慢性乙型肝炎患者外周血CD45~+T淋巴细胞亚群检测的临床意义

目的探讨慢性乙型肝炎患者外周血CD45~+T淋巴细胞亚群的特点及其与肝病病情的关系。方法对52例慢性乙型肝炎轻中度和48例慢性乙型肝炎重度以及50名健康人群的外周血进行CD3~+/CD4~+/CD8~+,CD4~+CD45RA~+、CD4~+CD45RO~+、CD8~+CD45RA~+、CD8~+CD45RO~+T淋巴细胞计数检测。结果CD3~+,CD4~+,CD4~+CD45RA~+,CD4~+CD45RO~+T淋巴细胞百分比在三组间差异无明显统计学意义(P0.05);CD8~+,CD8~+CD45RA~+,CD8~+CD45RO~+T淋巴细胞百分比三组间差异有统计学意义(P0.05)。结论乙型肝炎病毒感染过程中慢性化的发生CD8~+CD45RO~+T细胞起着重要作用,并且与病情进展呈正相关;CD3~+,CD4~+,CD4~+CD45RA~+、CD4~+CD45RO~+T淋巴细胞百分比不能有效地反映肝病的进展,CD8~+,CD8~+CD45RA~+、CD8~+CD45RO~+T淋巴细胞百分比联合检测能够更好地了解慢性乙型肝炎的发病原因和临床预后,从而指导临床。     

Expression and function of inducible costimulator on peripheral blood T cells in patients with systemic lupus erythematosus

OBJECTIVE: To investigate the role of inducible costimulator (ICOS) in the pathogenesis of SLE, we assessed its expression on peripheral blood CD4 and CD8 T cells and functional roles in patients with systemic lupus erythematosus (SLE). METHODS: Expression of ICOS on peripheral blood CD4 and CD8 T cells and ICOS ligand (ICOSL) on peripheral blood CD19 B cells from patients with SLE, patients with rheumatoid arthritis (RA) and healthy volunteers were determined by two-colour flow cytometry. The functional costimulatory effects of ICOS on peripheral blood mononuclear cells (PBMC) were assessed by T-cell proliferative responses, cytokines, anti-double-stranded DNA (anti-dsDNA) antibody and total IgG production. RESULTS: Peripheral blood CD4 and CD8 T cells expressing ICOS were significantly increased in patients with SLE compared with patients with RA and healthy subjects. Peripheral blood CD19 B cells expressing ICOSL in SLE were markedly reduced compared with RA. Proliferative responses of anti-CD3/ICOS costimulation were significantly higher than those of anti-CD3/hamster IgG (HIgG) in healthy subjects, but not in patients with SLE. Anti-CD3/ICOS-stimulated SLE PBMC secreted similar levels of IL-10 and IFN-gamma but a significantly lower level of IL-2 than healthy PBMC. Anti-CD3/ICOS-mediated costimulation significantly enhanced the production of anti-dsDNA antibodies and total IgG in patients with SLE. CONCLUSION: Hyperexpression of ICOS on peripheral blood CD4 and CD8 T cells from patients with SLE contributed to the dysregulated T-cell proliferation, T-cell activation and pathogenic autoantibody production, which showed that the abnormality of ICOS costimulation may play an immunopathological role(s) in the pathogenesis of SLE.     

梅毒与梅毒合并病毒性肝炎患者外周血T淋巴细胞亚群变化*

目的 调查梅毒及其合并病毒性肝炎患者外周血T淋巴细胞亚群的变化。方法 2016年1月～2020年6月我院收治的93例感染苍白螺旋体(TP)梅毒患者中,单纯梅毒感染61例,TP合并CHB患者21例和TP合并CHC患者11例,另选择健康体检者84例。使用流式细胞仪检测外周血T淋巴细胞亚群。结果 梅毒患者外周血CD3⁺、CD4⁺、CD4⁺CD45RO⁺和CD8⁺CD45RA⁺细胞百分比及CD4⁺/CD8⁺细胞比值分别为(52.2±8.5)%、(40.3±5.7)%、(18.1±3.9)%、(12.4±3.7)%和(1.2±0.3),均显著低于健康人[分别为(69.1±7.6)%、(50.7±6.9)%、(20.6±4.7)%、(16.2±4.3)%和(1.9±0.5),P＜0.05],而外周血CD8⁺、CD4⁺CD45RA⁺和CD8⁺CD45RO⁺细胞百分比显著高于健康人[分别为(32.4±7.3)%、(24.7±6.5)%和(8.7±1.5)%对(26.2±5.4)%、(21.8±6.2)%和(5.4±1.1)%,P＜0.05];三组外周血CD8⁺、CD4⁺CD45RA⁺、CD4⁺CD45RO⁺、CD8⁺CD45RA⁺和CD8⁺CD45RO⁺细胞百分比及CD4⁺/CD8⁺细胞比值比较,差异有统计学意义(P＜0.05),TP合并CHB组和TP合并CHC组患者外周血CD8⁺、CD4⁺CD45RA⁺和CD8⁺CD45RO⁺细胞百分比均显著高于TP组(P＜0.05),而TP合并CHB组和TP合并CHC组患者外周血CD4⁺/CD8⁺比值、CD4⁺CD45RO⁺和CD8⁺CD45RA⁺细胞百分比显著低于TP组(P＜0.05),TP合并CHB组与TP合并CHC组患者外周血CD8⁺、CD4⁺CD45RA⁺、CD4⁺CD45RO⁺、CD8⁺CD45RA⁺和CD8⁺CD45RO⁺细胞百分比及CD4⁺/CD8⁺细胞比值比较均无统计学差异(P＞0.05)。结论 梅毒患者存在显著的外周血淋巴细胞亚群变化,合并CHB或合并CHC患者细胞免疫功能变化更明显,其临床意义值得进一步探讨。     

Differential costimulation through CD137 (4-1BB) restores proliferation of human virus-specific "effector memory" (CD28(-) CD45RA(HI)) CD8(+) T cells

In healthy carriers of human cytomegalovirus (HCMV), the virus-specific memory CD8(+) T-cell population is often dominated by CD28(-) CD45RA(hi) cells that exhibit direct ex vivo cytotoxicity but whose capacity for proliferation and generation of further memory cells has been questioned. We show that when highly purified CD28(-) CD45RA(hi) CD8(+) T cells are stimulated with viral peptide presented by autologous monocytes, the virus-specific T cells show early up-regulation of CD137 (4-1BB) and CD278 (ICOS), re-express CD28, and proliferate with similarly high cloning efficiency in limiting dilution analysis as CD28(+) CD45RO(hi) cells or CD28(-) CD45RO(hi) cells. Using peptide-pulsed autologous fibroblasts transfected with individual costimulatory ligands as antigen presenting cells, we showed CD137L to be a key costimulatory ligand for proliferation of CD28(-) CD45RA(hi) CD8(+) T cells and not CD80, CD86, or CD275 (ICOSL). Therefore, CD28(-) CD45RA(hi) CD8(+) T cells were not terminally differentiated but required a specific costimulatory signal for proliferation.     

Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis

Systemic lupus erythematosus (SLE) is a complex autoimmune disease and lupus nephritis (LN) represents a major clinical manifestation. Studies have shown that elevated inducible co-stimulator (ICOS) in SLE. The purpose of the study was to investigate the expression of ICOS on T cells in patients with LN. Flow cytometry (FCM) was used to analyze the expression of ICOS on peripheral blood T lymphocytes in LN patients, SLE patients without nephritis, and healthy controls. The expression of ICOS on CD4 + CD45RO + and CD8 + CD4RO + T cells was significantly increased in SLE patients when compared with healthy controls (P < 0.001). In addition, ICOS expression in patients with nephritis was higher than those without nephritis (P < 0.01). Taken together, our results suggest that ICOS co-stimulatory pathway is important in the pathogenesis of LN; blockade of the pathway might represent a novel therapeutic strategy for the treatment of LN.     

Interleukin-10 expression: is there a neglected contribution of CD8+ T cells in rheumatoid arthritis joints?

OBJECTIVE: To search for RA specific processes among T cell accumulation, T cell activation, or cytokine expression in CD4+ and CD8+ synovial fluid (SF) T cells. METHODS: Flow cytometry of CD4+, CD8+, CD45RA+, CD45RO+, CD69 double or triple stained peripheral blood (PB) and SF T cells. IL-2, IL-10, and IFN-gamma expression was determined in PMA + ionomycin stimulated T cells on the single cell level. Concentrations of secreted IL-2, IL-4, IL-10, and IFN-gamma were quantified in the sera and synovial fluids by enzyme linked immunosorbent assay (ELISA). RESULTS: A preferential recruitment of CD45RO+ memory T cells was found for CD4+ helper T cells, and in similar also for CD8+ suppressor T cells. An elevated CD69 expression was detected in memory, but also in CD45RA+ naive CD4+ and CD8+ SF T cells, whilst IL-2 expression was only demonstrable in a minor proportion of T cells populations. Preferential recruitment of memory T cells, but incomplete activation of naive and memory, CD4+ and CD8+ T cells were in similar found in RA and control patients. In RA but not in the control patients, a relevant proportion of CD4+ and CD8+ PB and SF T cells expressed IL-10 and IFN-gamma. High concentrations of IL-10, that were correlated with the amounts of secreted TNF-alpha, were only detected in RA joints. CONCLUSION: Memory and naive T cell state of CD4+ and CD8+ T cell accumulates in the joints, and early T cell activation occur in similar patterns in RA and control patients. High IL-10 SF concentrations in contrast, and elevated percentages of IFN-gamma and IL-10 expressing CD4+ and CD8+ T cells in the PB and SF were characteristic for RA. Here, CD8+ T cells may contribute to high IL-10 concentrations in RA joints.     

Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-alpha inhibitors

OBJECTIVE: To explore the regulation of factors involved in lymphocyte trafficking in patients with rheumatoid arthritis (RA) undergoing treatment with tumour necrosis factor alpha (TNF-alpha) inhibitors. METHODS: We examined 14 consecutive patients with RA according to ACR criteria prior to and during treatment with TNF-alpha inhibitors (seven etanercept, seven infliximab) and determined disease activity using the Disease Activity Score (DAS-28). Peripheral blood mononuclear cells were isolated before and after 6 and 14 weeks of treatment and analysed immediately for CD3, CD4 and CD8, expression of chemokine receptors CXCR3 and CCR4, CD45RO phenotype and for expression of interferon gamma (IFN-gamma) and interleukin 4 (IL-4) using four-colour flow cytometry. RESULTS: We found significant increases in CD4 and CD8 T lymphocytes expressing CXCR3 after 6 and 14 weeks. The overall proportion of T lymphocytes expressing CCR4 appeared unchanged. More than half of peripheral CD4 T lymphocytes showed a memory phenotype (CD45RO), with a non-significant increase under TNF-alpha inhibition. Upon activation, up to 30% of CXCR3(+)/CD4 T cells expressed IFN-gamma, while IL-4-expressing cells were rare. There was a robust negative correlation between CXCR3(+)/CD4 T lymphocytes and DAS-28. CONCLUSIONS: TNF-alpha inhibition with infliximab and etanercept results in sustained accumulation of CXCR3 positive T lymphocytes in the peripheral blood of RA patients. This suggests altered lymphocyte trafficking during TNF-alpha inhibition.     

Cd28 expression on t cell subsets in vivo and cd28-mediated t cell response in vitro in patients with rheumatoid arthritis

Objective. In view of the critical importance of the CD28–CD80 (B7/BB1) costimulatory pathway in antigen-specific T cell activation and clonal expansion, we examined CD28 surface molecule expression in vivo, and T cell receptor/CD3-mediated and B7/BB1-costimulated T cell proliferation in vitro, in rheumatoid arthritis (RA). Methods. Two-color immunofluorescence analyses of peripheral blood and synovial fluid–derived T cells, as well as ³H-thymidine incorporation assays, were performed. Results. In the peripheral blood of 31 patients with active, untreated RA, a mean of 91% (range 48–100%) of CD4+ and 46% (range 13–82%) of CD8+ T cell subsets were CD28+, which was not significantly lower than normal. Although an overall decrease in the number of T cells was not observed, the numbers of CD28+CD8+ T cells were significantly lower in RA patients (mean 233/μl, versus 292/μl in controls), and this decrease was more pronounced in patients with severe disease (mean 172/μl). CD28 expression on peripheral CD8+ T cells in RA patients, but not in healthy individuals, correlated inversely with T cell activation as assessed by HLA–DR antigen expression. In contrast to the peripheral blood, RA synovial fluid T cells were almost exclusively CD28+, suggesting that migration of CD28+CD8+ T cells to active sites of inflammation may occur. In vitro proliferative responses of peripheral blood T cells to B7/BB1 costimulation in the presence of mitogenic doses of anti-CD3 monoclonal antibody were identical in patients with RA and healthy individuals. Conclusion. Functionally intact CD28+ T cells may contribute to the abnormal immunoregulation and joint inflammation in RA.     

Fas/Fas ligand expression and characteristics of primed CD45RO+ T cells in the inflamed mucosa of ulcerative colitis

BACKGROUND: Chronic immune activation in the colon is characteristic of ulcerative colitis (UC). Fas/Fas ligand (FasL) system is a mechanism responsible for activation-induced cell death (AICD), which maintains homeostasis within the immune system. Thus, Fas/FasL expression on activated colonic T cells of UC patients, as well as the susceptibility of such T cells to AICD was investigated in order to determine the role of activated colonic T cells in the long lasting inflammation in UC. METHODS: Fas, FasL, and CD45RO expression on peripheral blood and colonic T cells of UC patients were assayed by flow cytometry. Apoptosis of colonic T cells induced by anti Fas antibody was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. RESULTS: The majority of colonic T cells expressed both CD45RO and Fas in the colonic mucosa, a situation that was quite different from that in the peripheral blood. The number of CD45RO+CD8+ and Fas+CD8+ T cells was significantly lower in UC patients than the controls, unlike the number of Fas+CD4+ T cells. In contrast, the number of both CD45RO+CD4+ and CD45RO+CD8+ T cells in UC mucosa expressing FasL was significantly higher than in the controls. While Fas mediated apoptosis of CD45RO+CD8+ T cells was higher in UC patients than the controls, the number of apoptotic CD45RO+CD4+ T cells from UC mucosa was not. CONCLUSIONS: In UC patients, CD45RO+CD4+ T cells are less sensitive to apoptotic signals mediated by Fas. These phenomena may contribute to the pathogenesis of UC.