Low-avidity CD8lo T cells induced by incomplete antigen stimulation in vivo regulate naive higher avidity CD8hi T cell responses to the same antigen
Low-avidity CD8lo T cells induced by incomplete antigen stimulation in vivo regulate naive higher avidity CD8hi T cell responses to the same antigen
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DOI：
10.1002/eji.200535064
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发表时间：
2006-02-01
影响因子：
5.4
通讯作者：
Frelinger, JEA
中科院分区：
文献类型：
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作者：
Maile, R;Pop, SM;Frelinger, JEA
我们以前曾报道，多次注射与野生型HY肽组装的可溶性MHC-I类四聚体，会导致幼小雌性C57BL/6(136)小鼠对雄性皮肤移植物无反应。无反应性的诱导依赖于无反应性的同种异体CD8(10)T细胞群。CD8的表达减少通过限制有效信号转导的亲和力窗口来限制T细胞对HY肽的反应。我们和其他人已经证明，CD8(10)T细胞是CD8αβ(+)T细胞在体外和体内抗原刺激后的另一种稳定表型。我们发现CD8(10)T细胞在体外可以抑制初始CD8(+)T细胞对HY抗原的反应，并在体内抑制过继转移到女性受体后的男性皮肤移植排斥反应。这些新的调节性T细胞在抗原特异性刺激后表达表面转化生长因子β1，并分泌T细胞毒2细胞因子。抗转化生长因子-β抗体和潜伏期相关肽在体外可抑制这种抑制作用。我们还发现，HY特异性记忆CD8(+)T细胞克服了CD8(10)T细胞的调节。这些数据定义了一种新的外周调节性CD8(+)T细胞群，它是在体内反复遇到抗原后出现的。这些细胞与维持耐受性和记忆力有关。
We have previously reported that multiple injections of soluble MHC class I tetramers assembled with wild-type HY peptide induces unresponsiveness to male skin grafts in naive female C57BL/6 (136) mice. Induction of unresponsiveness is dependent on a population of unresponsive allospecific CD8(10) T cells. Reduced expression of CD8 acts to limit a T cell response to HY peptide by limiting the avidity window of effective signal transduction. We and others have demonstrated that CD8(10) T cells are an alternative stable phenotype of CD8 alpha beta(+) T cells in vitro and in vivo after antigen stimulation. We show here that CD8(10) T cells can suppress naive CD8(+) T cell responses to HY antigen in vitro and male skin graft rejection in vivo after adoptive transfer into female recipients. These novel regulatory T cells express surface TGF-beta 1 and secrete T cytotoxic 2 cytokines after antigen-specific stimulation. Anti-TGF-beta antibody and latency-associated peptide inhibit the suppressive effects in vitro. We also show that HY-specific memory CD8(+) T cells overcome regulation by CD8(10) T cells. These data define a novel peripheral regulatory CD8(+) T cell population that arises after repeated antigen encounter in vivo. These cells have implications in the maintenance of tolerance and memory.