Wing Kajsa, Onishi Yasushi, Prieto-Martin Paz, Yamaguchi Tomoyuki, Miyara Makoto, Fehervari Zoltan, Nomura Takashi, Sakaguchi Shimon
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Science. 2008 Oct 10;322(5899):271-5. doi: 10.1126/science.1160062.
Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells.
天然存在的Foxp3 + CD4 +调节性T细胞（Tregs）对于维持免疫自身耐受性和免疫稳态至关重要。在此，我们表明，Tregs中细胞毒性T淋巴细胞抗原4（CTLA-4）的特异性缺陷会导致小鼠全身性淋巴细胞增殖、致命的T细胞介导的自身免疫性疾病以及免疫球蛋白E的过度产生，并且还会产生强大的肿瘤免疫。Treg特异性CTLA-4缺陷会损害Tregs在体内和体外的抑制功能，特别是Treg介导的树突状细胞上CD80和CD86表达的下调。因此，天然Tregs可能严重需要CTLA-4通过影响抗原呈递细胞激活其他T细胞的能力来抑制免疫反应。
