T cells from epicutaneously immunized mice are prone to T cell receptor revision
T cells from epicutaneously immunized mice are prone to T cell receptor revision
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DOI：
10.1073/pnas.0409880102
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发表时间：
2005-02-22
影响因子：
11.1
通讯作者：
Janeway, CA
中科院分区：
文献类型：
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作者：
Bynoe, MS;Viret, C;Janeway, CA
T细胞受体(TCR)转基因(TG)小鼠的CD4(+)T细胞对髓鞘碱性蛋白(MBP)的AC1-11片段具有AC1-11特异性，可诱导出具有明显抑制/调节活性的T细胞，对AC1-11诱导的实验性自身免疫性脑脊髓炎具有保护作用。我们现在报道，这种抗病的MBP TCR TG小鼠也含有相当大一部分外周CD4(+)T细胞，缺乏TG TCRβ链的表面表达，并表达不同的、内源性重排的TCRβ链。在生理温度下体外孵育导致新的β链表达丧失，并回复到MBPαβTCR+表型。重组激活基因1和2蛋白的存在与有效的V(D)J重组活性一致。这些细胞的出现并不依赖于胸腺间隔。我们的结论是，在用自身抗原表面免疫的小鼠中，外周血特异性T细胞对多种耐受机制敏感。
Epicutaneous immunization of T cell receptor (TCR) transgenic (Tg) mice whose CD4(+) T cells are specific for the Ac1-11 fragment of myelin basic protein (MBP) with Ac1-11 elicits T cells with dominant suppressor/ regulatory activity that confers protection against Ac1-11-induced experimental autoimmune encephalomyelitis. We now report that such disease-resistant MBP TCR Tg mice also harbor a sizeable fraction of peripheral CD4(+) T cells lacking surface expression of the Tg TCR beta chain and expressing diverse, endogenously rearranged TCR beta chains. Ex vivo incubation at physiological temperature caused the loss of neo-beta-chain expression and reversion to the MBP alphabeta TCR+ phenotype. The presence of recombination activating gene 1 and 2 proteins in CD4+ T cells with revised TCRs was consistent with effective V(D)J recombination activity. The emergence of these cells did not depend on the thymic compartment. We conclude that in mice epicutaneously immunized with an autoantigen, peripheral specific T cells are susceptible to multiple mechanisms of tolerance.