内源性IL-17诱导MIP-2与IL-6表达在衣原体肺炎中促进中性粒细胞循环

目的 探讨衣原体肺炎中白细胞介素-17（interleukin -17,IL-17）对中性粒细胞（polymorphonuclear leucocyte,PMN）循环的调节作用及机制.方法 用40 μl含1×10^3包涵体形成单位（inclusion-forming units,IFU）的衣原体鼠肺炎株（Chlamydia muridarum,Cm）呼吸道感染BALB/c小鼠,诱导鼠衣原体肺炎.用抗鼠IL-17单克隆抗体吸入中和内源性IL-17,以相应独特型抗体（IgG2α）作为对照.用RT-PCR检测小鼠肺组织及肺上皮细胞系巨噬细胞炎性蛋白-2 （macrophage inflammatory protein-2,MIP-2）和IL-6 mRNA的表达.取小鼠支气管肺泡灌洗液细胞染色计数PMN,感染肺组织进行病理染色.结果 衣原体肺炎中,内源性IL-17中和小鼠肺组织PMN浸润显著降低,支气管肺泡灌洗液PMN数量显著低于对照组.IL-17与TNF-α协同可上调肺上皮细胞MIP-2和IL-6 mRNA表达,且内源性IL-17中和小鼠肺组织MIP-2和IL-6表达显著降低.结论 衣原体肺炎中IL-17通过促进肺组织细胞分泌趋化性细胞因子MIP-2和前症性细胞因子IL-6,诱导PMN循环,参与宿主抗衣原体炎性应答.     

乳杆菌肽聚糖对β-乳球蛋白致敏小鼠脾细胞Th1/Th2及Treg/Th17失衡的体外影响

【目的】观察嗜酸乳杆菌完整肽聚糖(Whole peptidoglycan,WPG)对致敏脾淋巴细胞Th1/Th2及Treg/Th17平衡的体外调节作用。【方法】通过腹腔注射β-乳球蛋白(β-Lg)建立BALB/c小鼠牛乳过敏模型。造模成功后,分离致敏小鼠的脾淋巴细胞并分别与不同剂量的WPG共同孵育,酶联免疫法检测细胞上清液中抗体(总IgE和特异性IgE),Th1/Th2及Treg/Th17相关细胞因子(IFN-γ,IL-4,TGF-β,IL-17)水平,流式细胞术检测脾淋巴细胞中CD3+、CD4+和CD8+的百分含量,荧光定量PCR法检测过敏小鼠脾细胞中Th1/Th2及Treg/Th17相关转录因子T-bet、GATA-3、Foxp3和RORγt mRNA的表达量。【结果】WPG体外刺激致敏脾细胞后可显著抑制IgE的产生,上调CD3+、CD4+细胞数及CD4+/CD8+比值,下调Th2型因子(IL-4,GATA-3mRNA)和Th17型因子(IL-17,RORγt mRNA)的表达,且与过敏组相比,中、高剂量WPG的作用效果显著(P0.05);另外,WPG体外作用还上调了Th1型因子(IFN-γ,T-bet mRNA)及Treg型因子(TGF-β,Foxp3 mRNA)的表达,且具有剂量依赖性。【结论】嗜酸乳杆菌WPG体外刺激可有效纠正致敏脾淋巴细胞的Th1/Th2及Treg/Th17失衡。     

沙眼衣原体感染诱导小鼠生殖道局部促炎性细胞因子的表达情况

建立小鼠生殖道沙眼衣原体感染模型,观察小鼠生殖道局部促炎性细胞因子的表达。将小鼠生物型沙眼衣原体C. muridarum 1＆#215;104 IFU阴道接种于C57B6背景雌性小鼠,取感染后阴道拭子做沙眼衣原体培养,计算IFU,监测小鼠感染和病原体清除情况;80 d后处死小鼠,检测子宫输卵管病理改变;ELISA检测感染过程中小鼠生殖道促炎性细胞因子IL-1α、IL-6、MIP-2和TNF-α产生情况。小鼠感染在第3至第15天维持较高水平,然后病原体被逐渐清除,整个病程约3~5周;病理检测显示子宫输卵有严重炎症、管腔扩张积水,狭窄等;于感染后第3天检测到局部IL-1α、IL-6、MIP-2分泌,第7天达高峰,然后逐渐下降至正常水平（ IL-6于11 d恢复正常,IL-1α和 MIP-2于15 d恢复正常）。 TNF-α仅在第7天检测到高水平表达。相对于TNF-α和IL-6,IL-1α和MIP-2维持时间较长。成功建立沙眼衣原体感染小鼠生殖道模型,沙眼衣原体急性感染可诱导小鼠生殖道局部分泌IL-1α、IL-6、MIP-2和TNF-α。     

肺炎支原体感染鼠T淋巴细胞活化的动态变化

动态观察肺炎支原体(Mycoplasma pneumoniae,Mp)感染鼠T淋巴细胞的数量及其亚群的变化,为正确评价T淋巴细胞在Mp感染中的作用提供理论依据。Mp滴鼻感染小鼠,在感染后不同时间点采集标本,流式细胞术检测感染鼠外周血中T淋巴细胞数量变化,ELISA测定脾细胞上清中TGF-β1、IL-10含量。结果表明,Mp感染不同时间点外周血中CD4+T淋巴细胞数量变化不明显或呈下降趋势。CD4+/CD8+比值下降。初次感染和再次感染的第3天、第7天,TGF-β1、IL-10表达水平升高。肺炎支原体感染对CD4+T淋巴细胞有一定抑制作用,外周血TGF-β1、IL-10的表达与脾细胞中CD4+T淋巴细胞数量变化成反比。提示TGF-β1可能参与了对Th1细胞的负调控作用。     

黄芪多糖对免疫抑制模型小鼠Treg细胞及Th17细胞亚群的影响

本研究旨在探讨黄芪多糖对免疫抑制模型小鼠CD4+CD25+调节性T细胞(Treg细胞)和CD4+Th17细胞亚群功能的影响。通过小鼠腹腔注射环磷酰胺建立免疫抑制动物模型,应用黄芪多糖对免疫抑制小鼠进行治疗,采用流式细胞仪分析脾脏中CD4+T细胞、CD4+CD25+Treg细胞的比例,ELISA检测血清IL-17的水平。结果表明:与模型对照组比较,黄芪多糖高、中剂量明显降低小鼠脾脏CD4+T细胞数的比例(P0.05),同时黄芪多糖上调小鼠脾脏CD4+CD25+Treg细胞数的比例(P0.05),降低免疫抑制小鼠血清IL-17的水平,尤其1.0 g/(kg·d)剂量组的IL-17水平下降较为明显(P0.01)。提示黄芪多糖具有提高免疫抑制小鼠CD4+CD25+Treg细胞数的比例、降低CD4+T细胞的数量及抑制IL-17分泌活性的作用。     

香菇多糖对急性弓形虫感染过程中CD4+CD25+Foxp3+调节性T细胞的调节作用研究

目的 探讨香菇多糖(Lentinan,Lent)对急性弓形虫感染BALB/c小鼠CD4+ CD25+ Foxp3+调节性T细胞(Tregs)数量和功能的调节作用.方法 对RH强毒株感染的BALB/c小鼠进行不同时间点的Lent预处理,动态观察用药后各组感染小鼠的生存率;在感染后第0、3、5、8和10天提取小鼠的脾细胞,FACS检测Tregs细胞数量的动态变化,ELISA法检测脾细胞培养上清中IL-10的分泌水平.结果 感染前6 d 1 mg/kg Lent用药组与药物未处理组相比显著提高了弓形虫感染小鼠的生存率;具有免疫抑制功能的Tregs数量于感染后8d达峰值,同时免疫应答中关键细胞因子IL-10的分泌水平也于感染后8d和10d显著增加.结论 对急性弓形虫感染的BALB/c小鼠采用Lent预处理之后能有效的调节Tregs的数量和功能,从而调控Th1/Th2之间的动态平衡达到治疗弓形虫的作用,为弓形虫病的临床治疗提供的新的理论依据.     

调节性T 细胞在发热结缔组织病患者外周血中的表达及临床意义

目的:研究Treg细胞在发热CTD患者外周血表达对结核感染的诊断价值。方法:对103例发热CTD患者进行T-SPOT.TB试验,将39例阳性者设为实验组-1,进行抗结核治疗,将64例阳性者设为实验组-2,另选取40例健康者作为对照组,检测三组外周血CD4+CD25+Treg细胞、Foxp3基因、IL-10、TGF-β的表达。结果:实验组CD4+CD25+Foxp3 Treg细胞占CD4+T比例高于对照组(P0.05),实验组-1治疗前外周血CD4+CD25+Foxp3 Treg细胞占CD4+T比例高于实验组-1治疗后、实验组-2(P0.05);实验组TGF-β表达量低于对照组(P0.05),实验组-1治疗前低于实验组-1治疗后及实验组-2(P0.05);实验组-1治疗前IL-10表达量低于实验组-1治疗后、实验组-2及对照组(P0.05)。结论:CD4+CD25+Foxp3 Treg细胞在发热CTD伴有结核感染患者外周血中的表达升高,其变化可作为结核感染诊断的辅助性指标。     

21例侵袭性肺曲霉病患者Th以及Treg细胞的检测

目的：分析侵袭性肺曲霉病患者辅助性T细胞（Th）以及调节性T细胞（Treg）在外周血中单个核细胞中的表达情况及其临床相关性,探讨Th和Treg细胞介导的免疫反应在侵袭性肺曲霉病中的作用。方法分离21例侵袭性肺曲霉病患者及19例健康人外周血的单个核细胞,采用流式细胞术分析Th1、Th2、Th17、Treg细胞群的表达情况,Real-timePCR方法检测相关转录因子T-bet、GATA-3、RORγt以及Foxp3的表达,ELISA法检测血清中相关细胞因子IFN-γ、IL-4、IL-17以及TGF-β的表达。结果与健康人对照组相比,侵袭性肺曲霉病患者Th1细胞以及Treg细胞占CD4＋T细胞的比例较之对照组明显降低;Th1、Th17、Treg细胞相关转录因子T-bet、RORγt、Foxp3以及相关细胞因子IFN-γ、IL-17A、TGF-β与对照组相比表达明显降低。结论IPA患者的Th1、Th17以及Treg细胞所介导的免疫反应受抑制。     

幽门螺杆菌感染者CD4~+ CD25~+调节性T细胞的检测及其相关性分析

目的检测幽门螺杆菌(Helicobacter pylori,H.pylori)感染阳性的胃部疾病患者外周血中CD4+CD25+调节性T细胞(Treg细胞)的百分含量及转化生长因子-β1(transforming growth factor-β1,TGF-β1)的水平,探讨CD4+CD25+调节性T细胞在H.pylori感染中的免疫调节作用及意义。方法采用流式细胞术检测H.pylori感染的慢性浅表性胃炎、胃癌前病变和胃癌患者外周血中CD4+CD25+调节性T细胞的含量、CD4+CD25+T细胞中表达FOXP3的细胞比例;并采用ELISA方法检测H.pylori感染者血清中TGF-β1的含量,无H.pylori感染的患者作为阴性对照。结果 H.pylori感染的患者外周血中CD4+CD25+调节性T细胞的百分含量及TGF-β1的水平较不伴有H.pylori感染的患者显著升高(P<0.05);H.pylori感染的浅表性胃炎、胃癌前病变及胃癌患者外周血中CD4+CD25+T淋巴细胞的百分含量及CD4+CD25+T细胞中表达FOXP3的细胞比例随病变严重程度的进展逐渐升高,差异有统计学意义(P<0.05);H.pylori感染的患者血清中TGF-β1水平也随病变严重程度的进展逐渐升高,差异有统计学意义(P<0.05)。结论 H.pylori感染可增加CD4+CD25+调节性T细胞的含量和TGF-β1的水平;随着病变严重程度的进展,CD4+CD25+调节性T细胞的含量和TGF-β1的水平逐渐升高,CD4+CD25+调节性T细胞百分含量和TGF-β1水平可作为临床判断病情进展的指标。     

CD8~+CD122~+T细胞在脑缺血过程中作用的研究

目的:探讨CD8+CD122+T细胞在脑缺血过程中的作用及其机制。方法:线栓法建立小鼠大脑中动脉栓塞模型(MCAO);激光共聚焦显微镜检测小鼠脑缺血组织中CD8+CD122+T细胞浸润情况;流式细胞仪检测脑缺血组织中CD8+CD122+T细胞/CD3+T细胞的比例及脾和胸腺中CD8+CD122+T细胞数量变化;RT-PCR方法检测CD8+CD122+T细胞对氧糖剥夺(Oxygen-glucose deprivation,OGD)条件下星形胶质细胞表达TNF-α,IL-1β,IFN-γ的影响。结果:各时间点脑缺血组织中均有CD8+CD122+T细胞浸润,且随脑缺血时间延长,缺血侧脑组织中CD8+CD122+T细胞/CD3+T细胞比例逐渐增加,5 d和7 d组差异显著,与非缺血侧相比,P5d0.05,P7d0.05;MCAO小鼠脾及胸腺中CD8+CD122+T细胞呈现先增高后降低的趋势。星形胶质细胞经OGD处理后,与对照组相比,IFN-γ、TNF-α、IL-1β表达显著增高,PIFN-γ0.01、PTNF-α0.001、PIL-1β0.01;CD122-blocked组与CD8+组相比,IFN-γ、TNF-α、IL-1β表达明显增高,PIFN-γ0.05、PTNF-α0.05、PIL-1β0.01;CD8+组与HBSS组相比,IFN-γ表达降低,P0.05;IL-1β表达有降低的趋势。结论:CD8+CD122+T细胞在脑缺血过程中发挥保护性作用,其保护作用通过CD122抑制星形胶质细胞TNF-α,IL-1β,IFN-γ炎症因子表达实现的。     

CD4+CD25+调节性T细胞的作用机制及临床应用

免疫应答通常是机体对各种异源物质的重要防御机制.但有些免疫应答会造成机体的损伤.近来,大量研究发现免疫系统内存在一类CD4 CD25 调节性T淋巴(CD4 CD25 regulatory T cell,CD4 CD25 TReg),在阻止大量免疫介导的疾病中起重要作用.该文从自身免疫耐受、维持T细胞自稳态、肿瘤免疫等方面介绍这类细胞的免疫调节作用.     

CD4+CD25+调节性T细胞

调节性T细胞(regulatory T cells,Treg)是机体维持自身耐受的重要组成部分。CD4^ CD25^ Treg细胞来源于胸腺,其主要功能是抑制自身反应性T细胞,并且其作用是通过直接的Treg-T效应细胞之间的相互接触方式来实现的。CD4^ CD25^ Treg细胞可分泌多种抑制性细胞因子,但与其抑制功能关系并不明确,目前有证据表明GITR和Foxp3与CD4^ CD25^ Treg细胞的抑制功能有关,并且Foxp3已作为CD4^ CD25^ Treg细胞的特异性标志。通过IL-10、TGF-β等抑制性细胞因子、imDC以及转基因技术可以产生具有免疫抑制功能的调节性T细胞。调节性T细胞在免疫相关性疾病、肿瘤免疫和抗感染免疫等方面具有重要意义。     

Non-regulatory CD8+CD45RO+CD25+ T-lymphocytes may compensate for the loss of antigen-inexperienced CD8+CD45RA+ T-cells in old age

The age-related decline in immune system functions is responsible for the increased prevalence of infectious diseases and the low efficacy of vaccination in elderly individuals. In particular, the number of peripheral naive T-cells declines throughout life and they exhibit severe functional defects at advanced age. However, we have recently identified a non-regulatory CD8+CD45RO+ CD25+ T-cell subset that occurs in a subgroup of healthy elderly individuals, who still exhibit an intact humoral immune response following influenza vaccination. Here, we demonstrate that CD8+CD45RO+CD25+ T-cells share phenotypic and functional characteristics with naive CD8+CD45RA+CD28+ T-cells from young individuals, despite their expression of CD45RO. CD8+CD45RO+ CD25+ T-cells also have long telomeres and upon antigenic challenge, they efficiently expand in vitro and differentiate into functional effector cells. The expanded population also maintains a diverse T-cell receptor repertoire. In conclusion, CD8+CD45RO+CD25+ T-cells from elderly individuals compensate for the loss of functional naive T-cells and may therefore be used as a marker of immunological competence in old age.     

Differential responses of CD4+CD45RA+ and CD4+CD29+ subsets to activated CD8+ cells: enhanced stimulation of the CD4+CD45RA+ subset by cells from patients with multiple sclerosis.

To examine whether functionally different CD4+ cells respond uniformly to the immunoregulatory influences of allogeneic activated CD8+ cells (*CD8+), we subfractionated the CD4+ population into two subsets, based on the high expression of either CD45RA or CD29. We confirmed that the CD45RA+ cells proliferated poorly in response to soluble anti-CD3 mAb, compared to the vigorous response obtained with the CD29+ subset; the CD45RA+ cells were more responsive to stimulation with Con A. Using normal healthy controls, we found that whereas *CD8+ had a significant suppressive effect on the proliferation of the CD29+ subset, they augmented the mitogen-induced proliferative response of the CD45RA+ cells. We further demonstrated that *CD8+ derived from MS patients augmented the response of the CD45RA+ subset to a significantly higher degree compared to healthy age- and sex-matched controls. There were no significant differences between the degree of suppression exerted by the *CD8+ of either the MS or the control group on the CD29+ cells. These results demonstrate that helper/memory CD4+CD29+ cells are more sensitive to the suppressive influences of *CD8+ compared to the CD4+CD45RA+ subset. In addition, in MS, *CD8+ may contribute to a more pronounced "on" signal for virgin CD4+CD45RA+ cells, which might serve as a means to perpetuate the autoimmune disease process.     

Follicular lymphoma intratumoral CD4+CD25+GITR+ regulatory T cells potently suppress CD3/CD28-costimulated autologous and allogeneic CD8+CD25- and CD4+CD25- T cells

Regulatory T cells (T(R)) play a critical role in the inhibition of self-reactive immune responses and as such have been implicated in the suppression of tumor-reactive effector T cells. In this study, we demonstrate that follicular lymphoma (FL)-infiltrating CD8+ and CD4+ T cells are hyporesponsive to CD3/CD28 costimulation. We further identify a population of FL-infiltrating CD4+CD25+GITR+ T(R) that are significantly overrepresented within FL nodes (FLN) compared with that seen in normal (nonmalignant, nonlymphoid hyperplastic) or reactive (nonmalignant, lymphoid hyperplastic) nodes. These T(R) actively suppress both the proliferation of autologous nodal CD8+CD25- and CD4+CD25- T cells, as well as cytokine production (IFN-gamma, TNF-alpha and IL-2), after CD3/CD28 costimulation. Removal of these cells in vitro by CD25+ magnetic bead depletion restores both the proliferation and cytokine production of the remaining T cells, demonstrating that FLN T cell hyporesponsiveness is reversible. In addition to suppressing autologous nodal T cells, these T(R) are also capable of suppressing the proliferation of allogeneic CD8+CD25- and CD4+CD25- T cells from normal lymph nodes as well as normal donor PBL, regardless of very robust stimulation of the target cells with plate-bound anti-CD3 and anti-CD28 Abs. The allogeneic suppression is not reciprocal, as equivalent numbers of CD25+FOXP3+ cells derived from either normal lymph nodes or PBL are not capable of suppressing allogeneic CD8+CD25- and CD4+CD25- T cells, suggesting that FLN T(R) are more suppressive than those derived from nonmalignant sources. Lastly, we demonstrate that inhibition of TGF-beta signaling partially restores FLN T cell proliferation suggesting a mechanistic role for TGF-beta in FLN T(R)-mediated suppression.     

Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis

CD4+CD25+ regulatory T cells can prevent and resolve intestinal inflammation in the murine T cell transfer model of colitis. Using Foxp3 as a marker of regulatory T cell activity, we now provide a comprehensive analysis of the in vivo distribution of Foxp3+CD4+CD25+ cells in wild-type mice, and during cure of experimental colitis. In both cases, Foxp3+CD4+CD25+ cells were found to accumulate in the colon and secondary lymphoid organs. Importantly, Foxp3+ cells were present at increased density in colon samples from patients with ulcerative colitis or Crohn's disease, suggesting similarities in the behavior of murine and human regulatory cells under inflammatory conditions. Cure of murine colitis was dependent on the presence of IL-10, and IL-10-producing CD4+CD25+ T cells were enriched within the colon during cure of colitis and also under steady state conditions. Our data indicate that although CD4+CD25+ T cells expressing Foxp3 are present within both lymphoid organs and the colon, subsets of IL-10-producing CD4+CD25+ T cells are present mainly within the intestinal lamina propria suggesting compartmentalization of the regulatory T cell response at effector sites.     

Analysis of the functional capabilities of CD3+CD4-CD8- and CD3+CD4+CD8+ human T cell clones

The functional capabilities of human peripheral blood CD3+CD4-CD8- and CD3+CD4+CD8+ T cell clones were examined. The clones were generated by culturing purified populations of CD3+CD4-CD8- and CD3+CD4+CD8+ T cells at limiting dilution (0.3 cell/well) in the presence of PHA, rIL-2, and irradiated PBMC as feeders. Twelve CD3+CD4-CD8- and 5 CD3+CD4+CD8+ clones were generated. Clonality was documented by analyzing TCR gamma- and beta-chain rearrangement patterns. All CD3+CD4-CD8- clones were stained by the TCR-delta 1 mAb that identifies a framework epitope of the TCR delta-chain, but not by mAb WT31 that identifies the TCR-alpha beta on mature T cells. In contrast, the CD3+CD4+CD8+ clones were all stained by WT31 and not by TCR-delta 1. All 17 clones were screened for various functional activities. Each secreted IL-2, IFN-gamma, and lymphotoxin/TNF-like factors when stimulated with immobilized mAb to CD3 (64.1), albeit in varying quantities. These clones secreted far less IL-2 and IFN-gamma than CD3+CD4+CD8- or CD3+CD4-CD8+ alpha beta expressing clones, but comparable amounts of lymphotoxin/TNF. All clones also functioned as MHC-unrestricted cytotoxic cells. This activity was comparable to that mediated by the CD3+CD4+CD8- or CD3+CD4-CD8+ alpha beta clones. Nine of 12 CD3+CD4-CD8- and 4 of 5 CD3+CD4+CD8+ clones were able to support B cell differentiation when activated by immobilized anti-CD3, but usually not as effectively as the CD3+CD4+CD8- or CD3+CD4-CD8+ alpha beta clones. The differences in the functional capabilities of the various clones could not be accounted for by alterations in the signaling capacity of the CD3 molecular complex as mAb to CD3 induced comparable increases in intracellular free calcium in each clone examined. When clones were stimulated with PWM, each suppressed B cell differentiation supported by mitomycin C-treated fresh CD4+ T lymphocytes. Suppression was dependent on the number of clone cells added to culture, but could be observed with as few as 12,500 cells per microtiter well. Phenotypic analysis of the clones revealed that all expressed CD29, CD11b, and the NKH1 surface Ag. These results demonstrate that the CD3+CD4-CD8- and CD3+CD4+CD8+ T cell clones exhibit many of the functional characteristics of mature T cells, although they produce IL-2 and IFN-gamma and provide help for B cell differentiation less effectively than CD3+CD4+CD8- and CD3+CD4-CD8+ alpha beta T cell clones.     

CD40L co-stimulation from CD8+ to CD4+ effector memory T cells supports CD4+ expansion

Effector memory T cells (T(EM)) have an important role in immunity against infection. However, little is known about the factors regulating T(EM) maintenance and proliferation. In this study, we investigated the role of direct interactions between CD4(+) and CD8(+) T cells (TC) for human T(EM) expansion. Proliferation of separated or mixed CD4(+) and CD8(+)T(EM) populations was analyzed after polyclonal stimulation in vitro. Compared to each isolated subset mixed T(EM) populations showed increased proliferation and expansion of both CD4(+) and CD8(+)T(EM) subpopulations. Combined activation of CD4(+) and CD8(+) memory T cells (Tmem) induced an increased expression of CD40L and CD40 on both populations. Subsequently, CD40/CD40L caused a bi-directional stimulation of CD40(+)CD4(+)T(EM) by CD40L(+)CD8(+)T(EM) and of CD40(+)CD8(+)T(EM) by CD40L(+)CD4(+)T(EM). Blocking of CD40L on activated CD8(+)T(EM) selectively inhibited proliferation of CD4(+)T(EM), while blocking of CD40L on CD4(+)T(EM) abrogated proliferation of CD8(+)T(EM). Taken together, we demonstrate for the first time that the expression of CD40L is exploited on the one hand by CD8(+)T(EM) to increase the proliferation of activated CD4(+)T(EM) and on the other hand by CD4(+)T(EM) to support the expansion of activated CD8(+)T(EM). Thus, efficient T(EM) expansion requires bi-directional interactions between CD4(+) and CD8(+)T(EM) cells.     

CD8+CD122+ regulatory T cells (Tregs) and CD4+ Tregs cooperatively prevent and cure CD4+ cell-induced colitis

We identified CD8(+)CD122(+) regulatory T cells (Tregs) and demonstrated their importance in the maintenance of immune homeostasis and in the recovery from experimental autoimmune encephalomyelitis. In this paper, we show that CD8(+)CD122(+) Tregs effectively prevent and cure colitis in a mouse model. In our experiments, colitis was induced in lymphocyte-deficient RAG-2(-/-) mice by transferring CD4(+)CD45RB(high) cells that were excluded with CD4(+) Tregs. Cotransfer of CD8(+)CD122(+) cells clearly suppressed the development of colitis, and this suppressive effect was similar to that of CD4(+)CD45RB(low) cells that were mostly CD4(+) Tregs. CD8(+)CD122(+) cells obtained from IL-10(-/-) mice were unable to suppress colitis, indicating that IL-10 is an important effect-transmitting factor in the suppression of colitis. CD8(+)CD122(+) cells showed a suppressive effect when they were transferred 4 wk after CD4(+)CD45RB(high) cells, indicating the therapeutic potential of CD8(+)CD122(+) cells. A mixture of CD8(+)CD122(+) cells and CD4(+)CD45RB(low) cells was far more effective than single Tregs, indicating the synergistic effect of these Tregs. These overall findings demonstrate the potential role of CD8(+) Tregs, and possibly together with CD4(+) Tregs, in the medical care of inflammatory bowel disease patients.