体外诱导小鼠胚胎干细胞分化为T淋巴细胞

目的 体外诱导小鼠胚胎干细胞(ESC)分化为T淋巴细胞. 方法 借助小鼠胚胎干细胞体外自然分化形成的类胚体(EB)中含有=三胚层细胞的独特细胞环境,加入多种细胞因子和胸腺肽α1,体外诱导小鼠ESC向T淋巴细胞分化.利用流式细胞仪在不同时间点检测诱导细胞表面T淋巴细胞发育相关的表面标志CD25、CD44、CD3、CD4、CD8以及T细胞受体(TCR)αβ和TCRγδ分子的表达水平. 结果 诱导3 d后,出现CD44+细胞;第6天出现CD44+、CD44+CD25+和CD25+细胞群;第15天开始表达CD3分子;1周后开始出现CD4+CD8+双阳性细胞.随着诱导时间的延长,CD3+细胞和CD4+CD8+细胞的百分比不断升高.培养1个月后,出现少量的CD4+和CD8+的单阳性细胞.诱导细胞早期表达TCRαβ和TCRγδ.随着诱导时间的延长,T细胞进一步成熟,诱导细胞以TCRαβT细胞为主. 结论 细胞因子和胸腺肽α1的共同作用可以在体外诱导小鼠胚胎干细胞分化成具有T淋巴细胞表型的细胞,且细胞的表型变化与T细胞体内正常的胸腺发育过程中的表型变化一致.     

γδT细胞的生物学意义

<正>T淋巴细胞表面可分别表达两种与CD3分子相关联的T细胞抗原受体(T cell re-ceptor,TCR):由α链和β链(TCRαβ)或γ链和δ链构成的异质二聚体.人们一直对αβT细胞的结构和功能研究予以很大程度上的关注,而对于γδT细胞研究投入要少些.主要原因可能是人们认为TCRγδ细胞是一个外周淋巴细胞库中的数量较小的亚群,不大可能在免疫应答中起主要作用.γδT细胞约占正常人外周血淋巴细胞总数的3%～10%,在其表面表达CD3分子,但绝大多数不表达CD4及CD8分子.然而在长期进     

肠管上皮内T细胞的来源、分布和组成

[日]／南野昌信／／临床免疫．－1996，28（2）．．265～268肠管上皮细胞间分布着淋巴细胞，称之为粘膜上皮间淋巴细胞（IEL）．小鼠末梢血T细胞几乎全部是TCRαβ，而IEL是由40％～70％TCRαβ细胞和30％～60％TCRγδ细胞组成．根据研究认为αβUEL的分化为胸腺依赖性（TD-IEL），γδIEL分化则是非胸腺依赖性（TI－IEL），αβIEL可以区分为CD8αβ+和CD8αα+两个亚型，前者可能为TD-IEL，后者是TI－IEL．利用裸鼠和胸腔搞出的铁合体小鼠观察胸腺对IEL分化的影响．结果，成熟小鼠搞出胸腺制备成俄合体小景时，在胸…     

敲除CD226通过调节小鼠脾脏和肠道免疫细胞比例缓解小鼠的慢性束缚应激引起的抑郁样行为

目的 探讨CD226在小鼠慢性束缚应激(CRS)诱导的抑郁样行为中发挥的免疫调控作用及其可能机制。方法 选取4～6周龄野生型(WT)雄性C57/BL6J和同品系CD226基因敲除(CD226KO)小鼠建立CRS模型，通过强迫游泳测试、蔗糖偏好测试等行为学检测方法对小鼠进行应激抑郁评分，利用流式细胞术分析脾脏、Peyer淋巴结及肠上皮内淋巴细胞亚群的差异。结果 与WT CRS组相比，CD226KO CRS组强迫游泳测试静止时间显著降低，蔗糖偏好率显著上升；脾脏CD4⁺T细胞和CD8⁺ T细胞之比显著降低；小肠上皮内淋巴细胞中T细胞受体αβ(TCRαβ)和TCRαβ CD8αβ细胞亚群比例显著升高。结论敲除CD226能够缓解小鼠CRS模型诱导的抑郁样行为，影响CRS状态下小鼠脾脏及肠道免疫细胞比例，改善小鼠应激状态下的整体免疫状态。     

川崎病患儿精细免疫分型分析及其临床意义

目的分析急性期川崎病(KD)患儿淋巴细胞各亚群的数量变化,探讨对临床诊治的意义。方法前瞻性分析重庆医科大学附属儿童医院收治的20例急性期KD患儿的临床资料以及外周血淋巴细胞各亚群(CD3~+、CD4~+及各亚群、CD8~+及各亚群、TCRαβ~+DNT、TCRγδ~+、CD4/CD8、CD19~+及各亚群、CD16~+CD56)的数量,并选取20例健康儿童为对照组,比较2组间的变化并分析临床指标与淋巴细胞各亚群的关系。结果 20例患儿的临床表现均符合典型KD的诊断标准,与对照组相比,KD组的CD8 naive、TCRαβ~+DNT、CD4/CD8、CD19~+及各亚群水平均明显升高(P0.05),而CD4 EM(CD4~+CD45RA-effector memory T cells)、CD4 Temra(CD4~+CD45RA~+effector memory T cells)、CD8~+T、CD8 CM(CD8~+CD45RA-central memory T cells)、CD8 Temra(CD8~+CD45RA~+effector memory T cells)、CD16~+CD56水平明显降低(P0.05)。有冠状动脉损害的KD患儿与未出现冠状动脉损害的KD患儿相比,TCRγδ~+T细胞水平明显升高(P0.05),CD4 Temra细胞水平有下降趋势。合并呼吸道或消化道系统并发症的KD患儿与未合并呼吸道或消化道系统并发症的KD患儿相比,CD3~+T、CD8 CM、CD8 EM、CD8 Temra细胞水平明显下降(P0.05),Transitional B细胞水平明显升高(P0.05)。结论急性期KD患儿的T、B淋巴细胞均处于异常活化的状态,其中TCRγδ~+T和CD4 Temra细胞与川崎病合并冠状动脉损害相关,CD3~+T、CD8 CM、CD8 EM、CD8 Temra和Transitional B细胞与川崎病合并呼吸道或消化道系统并发症相关。     

小鼠CD3+TCRαβ+CD4-CD8-胸腺细胞特性分析

目的分析CD3+TCRαβ+ DN(double negative)胸腺细胞的特性,推断其在胸腺发育中表型和功能的成熟过程. 方法分离纯化小鼠胸腺DN细胞,用多重染色的方法分析CD3+TCRαβ+ DN细胞的表型和TCR库,并与外周淋巴结的相应细胞进行对比. 结果 DN胸腺细胞为异质性细胞,包括CD3- DN细胞和CD3+ DN细胞,而CD3+ DN细胞又分为CD3+TCRαβ+和CD3+TCRγδ+ 2个亚群.其中,CD3+TCRαβ+ DN细胞体积较小,绝大部分细胞对可的松耐受,细胞中能与自身反应的Vβ3+和Vβ11+细胞比例极低,表型较为成熟,与髓质型SP(single positive)细胞相当. 结论 CD3+TCRαβ+ DN细胞不同于CD3-TCRαβ- DN细胞,是一个独特的细胞亚群,只有在经历表型和功能的进一步成熟后才能迁出胸腺,移至外周.     

肠道菌群失调增加小鼠肠上皮内T淋巴细胞活化和促炎细胞因子分泌

目的探讨肠道菌群失调对小鼠小肠上皮间淋巴细胞(i IEL)功能的影响。方法口服给予广谱抗生素头孢曲松钠造成菌群失调小鼠模型,用乙二胺四乙酸(EDTA)和二硫苏糖醇(DTT)消化上皮细胞,流式细胞术鉴定i IEL表型和T细胞亚群的比例,ELISA检测肠腔冲洗液中白细胞介素2(IL-2)、IL-6、γ干扰素(IFN-γ)水平,采用选择性培养基以及PCR检测肠道细菌的类别。结果与正常组相比,给予头孢曲松钠后小鼠肠道内细菌明显减少,真菌和酵母菌增多;i IEL中T淋巴细胞亚群的比例发生变化,其中γδT细胞比例明显升高;CD3+T细胞、CD8+T细胞以及T细胞受体(TCR)γδ+T细胞活化增加,肠腔内IL-2、IL-6、IFN-γ水平显著升高。结论肠道菌群失调导致定植抗力下降,真菌增多,微生物屏障功能被破坏,引起i IEL中T细胞活化增加,促炎细胞因子分泌增加,可能是菌群紊乱引起炎症性肠病的原因之一。     

丙酮酸激酶M2缺失不影响TCRαβ~+T细胞的增殖、活化、分化和抗肿瘤能力

为探究丙酮酸激酶M2(pyruvate kinase M2, PKM2)在TCRαβ~+T细胞中的功能,研究制备了TCRαβ~+T细胞条件性敲除PKM2小鼠。FACS检测发现PKM2缺失不影响小鼠外周淋巴器官中TCRαβ~+CD4~+与CD8~+T细胞百分比、增殖能力及活化潜能。TCRαβ~+T细胞特异性PKM2~(-/-)小鼠可在结肠组织中形成正常的Th1与Th17亚群,也可在体内外诱导产生正常的Th1与Th17。PKM2缺失同样不影响MC38移植瘤生长,也不改变移植瘤中TCRαβ~+CD4~+/CD8~+T细胞比例和T细胞IFN-γ的表达。因而,TCRαβ~+T细胞特异性PKM2~(-/-)小鼠具有正常的T细胞功能亚群。Western blotting表明,PKM2~(-/-)TCRαβ~+CD4~+与CD8~+T细胞中PKM1表达上调。据此,作者推测PKM1部分代偿了PKM2在TCRαβ~+T细胞中的生理功能。     

TCRαβ+CD8αα+上皮间淋巴细胞的肠道生活史

小鼠的小肠上皮定植着大量TCRαβ+CD8αα+上皮间淋巴细胞(IELs),该群细胞离开胸腺后直接定植于肠道上皮.肠道中的多种细胞因子、营养素、抗原等能直接作用于该群细胞,调节其表型、分化及功能.另外,其还能通过细胞膜表面分子与肠上皮细胞发生相互作用,从而维持对肠上皮细胞的免疫耐受状态.近年有研究表明,该群细胞在肠道炎症中主要发挥保护性作用,这为结肠炎等肠道炎症性疾病的治疗提供了新思路.     

人T细胞抗原受体基因的命名

<正>人T细胞抗原受体(TCR)是由二硫键连接的二条多肽链(αβ或γδ)经组成的异二聚体,属lg基因超家族,每条链具有与lg分子相似的V区、D区(仅对β和δ链)J区和C区.根据TCR的不同,可将T细胞分为αβ~+T细胞和γδ~+T细胞.人外周血中95%的T细胞为αβ~+TCR,其配体是MHC-抗原肽复合物;而γδ~+TCR一般仅表达于CD4~-CD8T细胞,这些γδ~+T细胞识别的抗原结构目前尚不清楚,但在机体抗感染免疫和抗肿瘤免疫中发挥着重要的作用.从胸腺内的发育过程来看,αβ~+T细胞和γδ~+T细胞可能来源于同一祖先,而且γδTCR的表达要早于αβTCR,分别相当于妊娠第九周和第十周.     

Human intraepithelial lymphocytes

The location of intraepithelial lymphocytes (IEL) between epithelial cells, their effector memory, cytolytic and inflammatory phenotype positions them to kill infected epithelial cells and protect the intestine against pathogens. Human TCRαβ⁺CD8αβ⁺ IEL have the dual capacity to recognize modified self via natural killer (NK) receptors (autoreactivity) as well as foreign antigen via the T cell receptor (TCR), which is accomplished in mouse by two cell subsets, the naturally occurring TCRαβ⁺CD8αα⁺ and adaptively induced TCRαβ⁺CD8αβ⁺ IEL subsets, respectively. The private/oligoclonal nature of the TCR repertoire of both human and mouse IEL suggests local environmental factors dictate the specificity of IEL responses. The line between sensing of foreign antigens and autoreactivity is blurred for IEL in celiac disease, where recognition of stress ligands by induced activating NK receptors in conjunction with inflammatory signals such as IL-15 can result in low-affinity TCR/non-cognate antigen and NK receptor/stress ligand interactions triggering destruction of intestinal epithelial cells.     

Control of the development of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β

The molecular mechanisms that direct the development of TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes (IELs) are not thoroughly understood. Here we show that transforming growth factor-β (TGF-β) controls the development of TCRαβ+CD8αα+ IELs. Mice with either a null mutation in the gene encoding TGF-β1 or T cell-specific deletion of TGF-β receptor I lacked TCRαβ+CD8αα+ IELs, whereas mice with transgenic overexpression of TGF-β1 had a larger population of TCRαβ+CD8αα+ IELs. We observed defective development of the TCRαβ+CD8αα+ IEL thymic precursors (CD4?CD8?TCRαβ+CD5+) in the absence of TGF-β. In addition, we found that TGF-β signaling induced CD8α expression in TCRαβ+CD8αα+ IEL thymic precursors and induced and maintained CD8α expression in peripheral populations of T cells. Our data demonstrate a previously unrecognized role for TGF-β in the development of TCRαβ+CD8αα+ IELs and the expression of CD8α in T cells.     

The expansion and selection of T cell receptor αβ intestinal intraepithelial T cell clones

In conventional mice, the T cell receptor (TCR)αβ⁺ CD8αα⁺ and CD8αβ⁺ subsets of the intestinal intraepithelial lymphocytes (IEL) constitute two subpopulations. Each comprise a few hundred clones expressing apparently random receptor repertoires which are different in individual genetically identical mice (Regnault, A., Cumano, A., Vassalli, P., Guy-Grand, D. and Kourilsky, P., J. Exp. Med. 1994. 180: 1345). We analyzed the repertoire diversity of sorted CD8αα and CD8αβ⁺ IEL populations from the small intestine of individual germ-free mice that contain ten times less TCRαβ⁺ T cells than conventional mice. The TCRβ repertoire of the CD8αα and the CD8αβ IEL populations of germ-free adult mice shows the same degree of oligoclonality as that of conventional mice. These results show that the intestinal microflora is not responsible for the repertoire oligoclonality of TCRαβ⁺ IEL. The presence of the microflora leads to an expansion of clones which arise independently of bacteria. To evaluate the degree of expansion of IEL clones in conventional mice, we went on to measure their clone sizes in vivo by quantitative PCR in the total and in adjacent sections of the small intestine of adult animals. We found that both the CD8αα and the CD8αβ TCRαβ IEL clones have a heterogeneous size pattern, with clones containing from 3 × 10³ cells up to 1.2 × 10⁶ cells, the clones being qualitatively and quantitatively different in individual mice. Cells from a given IEL clone are not evenly distributed throughout the length of the small intestine. The observation that the TCRαβ IEL populations comprise a few hundred clones of very heterogeneous size and distribution suggests that they arise from a limited number of precursors, which may be slowly but continuously renewed, and undergo extensive clonal expansion in the epithelium.     

Complexity of the mouse gut T cell immune system: Identification of two distinct natural killer T cell intraepithelial lineages

Gut thymo-dependent (CD8α⁺β⁺ or CD4⁺) or -independent (CD8α⁺β⁻) intraepithelial lymphocytes (IEL) mediate cytotoxicity following T cell receptor (TCR)-CD3 signaling, but only TCRγδ⁺ and αβ⁺ thymo-independent IEL show cytotoxicity of natural killer (NK) and antibody-dependent cell-mediated cytotoxicity types. Moreover, TCRαβ⁺ and γδ⁺ thymo-independent IEL express NK receptors, and may therefore be referred to as NK-TIEL. NK-TIEL cytotoxicity is mediated through perforin, Fas, or both pathways. In contrast to that of other NK cells, this cytotoxicity is not negatively regulated by signals delivered through the recognition of major histocompatibility complex class I molecules. Thus, gut IEL include T cell subsets with unique specificities and functions, ontogenically distinct from other T cell lineages, which may increase the antigenic repertoire diversity of the immune system participating in the defense of the epithelial barrier.     

FTY720对小肠移植物中淋巴细胞及单核细胞浸润的影响

目的：研究FTY720对同种异体小鼠小肠移植排斥反应的作用及可能机制。方法：以C3H小鼠（H-2k）为供者，C57BL/6小鼠(H-2b）为受者，行异位小肠移植。分别建立FTY720治疗组、空白对照组及同系移植组，在移植后6 d与12 d进行组织学观测评定排斥分数，流式细胞术分析移植物肠系膜淋巴结（MLN）、派氏结（PP）、粘膜上皮细胞间淋巴组织（IEL）与固有层淋巴组织（LPL）中淋巴细胞中受者淋巴细胞及单核细胞浸润情况。结果：FTY720在移植后6 d可有效抑制排斥反应，但在移植后14 d，排斥反应仍可发生在空白对照组，移植后6 d移植物内受者淋巴细胞基本取代供者细胞；而在FTY720治疗组，受者淋巴细胞进入移植物的速度及数量明显减缓，包括CD4+与CD8+ T细胞，以及CD19+ B细胞。受者来源的γδT淋巴细胞也显著减少。FTY720对Gr1+CD11b+单核细胞系也有一定的抑制作用。结论：FTY720可通过减少受者淋巴细胞及单核细胞进入移植小肠，起到缓解排斥反应的作用。     

Differential contribution of Lck and Fyn protein tyrosine kinases to intraepithelial lymphocyte development

The developmental stages and the role of protein tyrosine kinases (PTK) in the maturation of CD3⁺CD8αα⁺ intraepithelial lymphocytes (IEL) have not been extensively characterized. However, comparisons of thymic and extrathymic T cell development indicate that these processes involve some distinct signaling and selection events. We used mice deficient in Lck, Fyn, or both Lck and Fyn to analyze the role that these src-family PTK play in IEL development. In contrast to thymocyte development, we found that all IEL subsets develop in mice deficient for either kinase alone. However, lck^-/- animals exhibited reduced numbers of TcRαβ⁺CD8αα⁺ IEL, indicating that Lck is important in the development of these cells. Mice which lack both Lck and Fyn fail to generate TcRαβ⁺ IEL, suggesting that signaling through the preTcR, mediated by Lck and, to a lesser extent Fyn, is required for maturation of all TcRαβ⁺ IEL lineages. Interestingly, a small population of TcRγδ⁺CD8αα⁺ cells are apparent in lck^-/-fyn^-/- animals, demonstrating that TcRαβ⁺CD8αα⁺ and TcRγδ⁺CD8αα⁺ IEL have distinct PTK requirements for their development or expansion. CD3^?-CD8α^?CD44⁺ and CD3^?CD8αα⁺CD16/32⁺B220⁺ cells comprise the majority of IEL in both lck^-/-fyn^-/- and rag^-/- mice, while they are poorly represented in wild-type controls. Comparison of the cell surface phenotype of these putative precursor IEL in lck^-/-fyn^-/- and rag^-/- animals suggests that IEL maturation in these animals is arrested at an equivalent developmental stage. Overall, the data presented demonstrate that signals mediated by Lck or Fyn direct TcRαβ⁺CD8αα⁺ IEL maturation but are dispensable for the development of TcRγδ⁺CD8αα⁺ IEL.     

Late postnatal expansion of self-reactive CD8alphaalpha+ intestinal intraepithelial lymphocytes in mice

The intestinal epithelium is unique in that it harbors auto-reactive T cells largely absent from the peripheral TCR repertoire in normal mice. Intestinal intraepithelial lymphocytes (IEL) expressing self-reactive TCR are mostly CD8alphaalpha+ cells in adult H-Y TCR RAG(-/-) male mice homozygous for the restricting MHC I allele, H-2D(b). By contrast, in male mice heterozygous for the restricting and non-restricting MHC I allele, H-2D(d) (MHC F(1), H-2D(b/d)), IEL are composed of CD8alphabeta and CD8alphaalpha+ T cells. Here we demonstrate that IEL in the immediate postnatal period of MHC homozygous male mice were mostly CD8(-) T cells, while IEL in MHC F(1) male mice were CD8(-) and CD8alphabeta+ T cells. Regardless of the MHC I configuration and the ability to support positive selection of CD8alphabeta+ cells in the thymus, the expansion of CD8alphaalpha+ IEL was a late postnatal event that followed a reduction in CD8(-) IEL. Furthermore, although in vivo treatment with the specific peptide antigen resulted in an earlier accumulation of activated IEL, the expansion of CD8alphaalpha+ IEL remained inefficient until late in postnatal life. Finally, as CD8(-) IEL stimulated with TCR agonists in vitro, acquired expression of CD8alphaalpha, we propose that CD8alphaalpha+ IEL derive from CD8(-) IEL intermediates. Whether CD8(-) IEL are CD8alphabeta-lineage cells that escape deletion in the thymus or are T cells targeted to the intestine from the thymus because of the early and high level TCR transgene expression in this model, is not clear. The signals required for the expansion of CD8alphaalpha+ IEL are however, incomplete in the immediate postnatal intestine. Determining the factors required for the expansion or retention of CD8alphaalpha+ IEL bearing high affinity, self-specific TCR will further elucidate the in vivo role of these T cells in intestinal homeostasis and perhaps, autoimmunity.     

Microbial colonization influences composition and T-cell receptor V beta repertoire of intraepithelial lymphocytes in rat intestine.

Studies in mice have shown that the composition of intestinal intraepithelial lymphocytes (IEL) may be markedly altered by gut microbial colonization. Such modulation was studied in a rat model by the use of germ-free and conventionalized animals from which IEL from the small intestine were isolated and analysed by flow cytometry. Conventionalization caused expansion as well as phenotypic alterations of T-cell receptor (TCR) alpha/beta + IEL in that the proportions of CD4+ and CD8 alpha beta + TCR alpha/beta + cells were increased, while the double negative (CD4- CD8-) fraction was reduced. microbial colonization also influenced the TCR V beta repertoire of CD8+ IEL in that the proportions of V beta 8.2+ and V beta 10+ cells were increased, whereas V beta 8.5+ and V beta 16+ cells were relatively decreased. Moreover, conventionalization influenced the levels of TCR cell surface expression in the same V beta subsets. Three-colour flow-cytometric analysis demonstrated that skewing of the V beta repertoire was most pronounced in the CD8 alpha alpha + subset, although the numerical increase of IEL mainly included the CD8 alpha beta + subset. In contrast to IEL, the TCR V beta repertoire in mesenteric lymph nodes was unchanged after intestinal colonization. These results confirm that TCR alpha/beta + IEL subpopulations respond dynamically to the microbial gut flora and suggest that their V beta repertoire can be shaped by luminal microbial antigens.     

Evaluation of the immunoregulatory activity of intraepithelial lymphocytes in a mouse model of chronic intestinal inflammation

Intraepithelial lymphocytes (IELs) represent the first line of lymphocyte defense against the intestinal bacteria. Although previous studies have demonstrated a protective role of IELs in the development of colitis, the data supporting a regulatory role for IELs are limited. The objective of this study was to examine the suppressive activity of IELs in vitro and in vivo using a mouse model of chronic small and large bowel inflammation. Adoptive transfer of CD8α(+) IELs isolated from small intestines of wild-type (WT) mice into TCR βxδ-deficient (TCR βxδ(-/-)) recipients did not prevent or delay the onset of the disease induced by WT CD4(+)CD45RB(high) T cells. On the contrary, we observed a more rapid onset of wasting and clinical signs of intestinal inflammation when compared with animals injected with CD4(+)CD45RB(high) T cells alone. Histopathological scores of small and large bowel did not differ significantly between the two groups. Transfer of IELs alone did not produce any pathological changes. Real-time PCR analysis of intestinal tissues showed up-regulation of message for T(h)1- and macrophage-derived cytokines in colon and small bowel. Using Foxp3-GFP reporter mice, we were unable to detect any Foxp3(+) cells within the CD8α(+) IELs but did find a small population of Foxp3(+)CD4(+) IELs in the small and large bowel. Using in vitro suppression assay, we found that neither TCRαβ(+)CD8αα(+), TCRαβ(+)CD8αβ(+) nor TCRγδ(+)CD8αα(+) IELs were capable of suppressing CD4(+) T-cell proliferation. Taken together, our data do not support an immunoregulatory role for CD8α(+) IELs in a mouse model of small and large bowel inflammation.     

Regulatory functions for murine intraepithelial lymphocytes in mucosal responses

Our studies have given direct evidence that CD3+, CD4-, CD8+ T cells in the IELs can be separated into at least two subsets that produce IFN-gamma and/or IL-5 and may exhibit Th1- and Th2-type functions in the epithelium and in the underlying lamina propria region. Further, it was also shown that TCR1+ T cells in IELs are capable of producing IFN-gamma and/or IL-5. In addition to production of these cytokines, IELs derived from mice orally primed with TD antigen contain a subset of T cells which possess antigen-specific immunoregulatory function. CD3+, CD4-, CD8+ T cells isolated from IEL of TD antigen-primed mice abrogated systemic unresponsiveness to secondary-type responses including those of the IgA isotype upon adoptive transfer to mice with OT. Our studies further suggested that these CD3+, CD4-, CD8+ IELs use the gamma-delta form of TCR (TCR1) for their immunoregulatory function.