Zheng Yong, Manzotti Claire N, Liu Michael, Burke Fiona, Mead Karen I, Sansom David M
Medical Research Council Center for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom.
J Immunol. 2004 Mar 1;172(5):2778-84. doi: 10.4049/jimmunol.172.5.2778.
Regulatory T cells (Treg) are important in maintaining tolerance to self tissues. As both CD28 and CTLA-4 molecules are implicated in the function of Treg, we investigated the ability of their two natural ligands, CD80 and CD86, to influence the Treg-suppressive capacity. During T cell responses to alloantigens expressed on dendritic cells, we observed that Abs against CD86 potently enhanced suppression by CD4(+)CD25(+) Treg. In contrast, blocking CD80 enhanced proliferative responses by impairing Treg suppression. Intriguingly, the relative expression levels of CD80 and CD86 on dendritic cells are modulated during progression from an immature to a mature state, and this correlates with the ability of Treg to suppress responses. Our data show that CD80 and CD86 have opposing functions through CD28 and CTLA-4 on Treg, an observation that has significant implications for manipulation of immune responses and tolerance in vivo.
调节性T细胞（Treg）在维持对自身组织的耐受性方面起着重要作用。由于CD28和CTLA-4分子都与Treg的功能有关，我们研究了它们的两种天然配体CD80和CD86影响Treg抑制能力的作用。在T细胞对树突状细胞上表达的同种异体抗原的反应过程中，我们观察到抗CD86抗体能显著增强CD4(+)CD25(+) Treg的抑制作用。相反，阻断CD80会通过损害Treg的抑制作用而增强增殖反应。有趣的是，在从未成熟状态向成熟状态转变的过程中，树突状细胞上CD80和CD86的相对表达水平会发生调节，这与Treg抑制反应的能力相关。我们的数据表明，CD80和CD86通过CD28和CTLA-4对Treg具有相反的作用，这一观察结果对体内免疫反应和耐受性的调控具有重要意义。
