SELECTION OF INTRAEPITHELIAL LYMPHOCYTES WITH CD8 ALPHA ALPHA CO-RECEPTORS BY SELF-ANTIGEN IN THE MURINE GUT

SELECTION OF INTRAEPITHELIAL LYMPHOCYTES WITH CD8 ALPHA ALPHA CO-RECEPTORS BY SELF-ANTIGEN IN THE MURINE GUT
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DOI:
10.1073/pnas.89.12.5336
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发表时间:
1992-06-15
影响因子:
11.1
通讯作者:
GUYGRAND, D
GUYGRAND, D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ROCHA, B;VONBOEHMER, H;GUYGRAND, D

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我们研究了T细胞受体(TCR)和α/α CD 8表达的胸腺非依赖性上皮内淋巴细胞(TI IEL)从小鼠肠道携带转基因(TG)TCR α-β特异性的男性抗原,提出的H-2D(B)I类主要组织相容性复合体(MHC)分子。与在胸腺中分化的TCR+ α-β细胞(从CD 4 + CD 8+前体到CD 4 + CD 8-或CD 4-CD 8+子代)相反,TI IEL不被自身抗原删除,在不存在特异性肽的情况下它们也不被阳性选择。相反,在自身MHC的背景下识别抗原是CD 8 + TI IEL的选择和颗粒分化所需的。我们的研究结果还表明,与胸腺相反,β-TG的表达不会阻断TI IEL中内源性TCR γ-δ基因的表达。这个肠道IEL亚群的大小及其在库选择机制上的差异表明T细胞分化的主要胸腺外途径的存在,其作用仍有待阐明。
We have studied T-cell receptor (TCR) and alpha/alpha CD8 expression in thymus-independent intraepithelial lymphocytes (TI IELs) from the gut of mice bearing transgenic (TG) TCR alpha-beta specific for the male antigen, presented by H-2D(b) class I major histocompatibility complex (MHC) molecules. In contrast to TCR+ alpha-beta cells differentiating in the thymus (from CD4+CD8+ precursors to CD4+CD8- or CD4-CD8+ progeny), TI IELs are not deleted by self-antigens, nor are they positively selected in the absence of the specific peptide. On the contrary, recognition of the antigen in the context of self-MHC is required for selection and granular differentiation of CD8+ TI IELs. Our results also show that, in contrast to the thymus, expression of the beta-TG does not block expression of endogenous TCR gamma-delta genes in TI IELs. The size of this gut IEL subpopulation and its difference in mechanisms of repertoire selection demonstrate the existence of a major extrathymic pathway of T-cell differentiation, the role of which remains to be elucidated.