CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism.
CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism.
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DOI：
10.1172/jci19727
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发表时间：
2004-01
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影响因子：
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通讯作者：
Z. Dai;Qi Li;Yinong Wang;G. Gao;Lonnette Diggs;G. Tellides;Fadi G Lakkis
中科院分区：
文献类型：
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作者：
Z. Dai;Qi Li;Yinong Wang;G. Gao;Lonnette Diggs;G. Tellides;Fadi G Lakkis
CD 4（+）CD 25（+）调节性T（Treg）细胞抑制幼稚T细胞应答，防止自身免疫，并延迟同种异体移植物排斥。然而，Treg细胞是否抑制记忆T细胞介导的同种异体移植排斥尚不清楚，因为后者比它们的幼稚对应物产生更快和更强的免疫应答。在这里，我们发现抗原诱导的Treg细胞（而非初始Treg细胞）抑制由记忆性CD 8（+）T细胞介导的同种异体移植排斥反应。抑制是同种异体特异性的，因为第三方抗原诱导的Treg细胞不会延迟同种异体排斥反应。体内和体外分析显示，抗原诱导的Treg细胞存在时，同种异体记忆性CD 8（+）T细胞的凋亡显著增加，而其增殖不受影响。重要的是，当Treg细胞缺乏CD 30或用抗CD 30配体Ab阻断CD 30配体-CD 30相互作用时，既没有观察到同种异体移植排斥反应的抑制，也没有观察到记忆性CD 8（+）T细胞凋亡的增强。因此，这项研究提供了直接的证据，致病性记忆T细胞是服从于抗原特异性的方式抑制，并确定CD 30作为一个分子，这是至关重要的记忆T细胞反应的调节。
CD4(+)CD25(+) regulatory T (Treg) cells suppress naive T cell responses, prevent autoimmunity, and delay allograft rejection. It is not known, however, whether Treg cells suppress allograft rejection mediated by memory T cells, as the latter mount faster and stronger immune responses than their naive counterparts. Here we show that antigen-induced, but not naive, Treg cells suppress allograft rejection mediated by memory CD8(+) T cells. Suppression was allospecific, as Treg cells induced by third-party antigens did not delay allograft rejection. In vivo and in vitro analyses revealed that the apoptosis of allospecific memory CD8(+) T cells is significantly increased in the presence of antigen-induced Treg cells, while their proliferation remains unaffected. Importantly, neither suppression of allograft rejection nor enhanced apoptosis of memory CD8(+) T cells was observed when Treg cells lacked CD30 or when CD30 ligand-CD30 interaction was blocked with anti-CD30 ligand Ab. This study therefore provides direct evidence that pathogenic memory T cells are amenable to suppression in an antigen-specific manner and identifies CD30 as a molecule that is critical for the regulation of memory T cell responses.