Department of Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Immunol. 2012 Aug 1;189(3):1123-7. doi: 10.4049/jimmunol.1200695. Epub 2012 Jul 2.
CTLA-4 is thought to inhibit effector T cells both intrinsically, by competing with CD28 for B7 ligands, and extrinsically, through the action of regulatory T cells (Tregs). We studied in vivo responses of normal and CTLA-4-deficient Ag-specific murine effector CD4(+) T cells. We directly demonstrate that effector T cell-restricted CTLA-4 inhibits T cell responses in a cell-extrinsic manner. Cotransfer experiments show that CTLA-4 on normal effector CD4(+) T cells completely abrogates the dramatically increased expansion normally experienced by their CTLA-4-deficient counterparts. Neither the wild-type nor the CTLA-4-deficient T cells express the Treg transcription factor Foxp3 when transferred alone or together. Thus, cell-extrinsic inhibition of T cell responses by CTLA-4 is not limited to Tregs but is also a function of effector T cells.
CTLA-4 被认为通过与 CD28 竞争 B7 配体内在地抑制效应 T 细胞，并且通过调节性 T 细胞 (Tregs) 外在地抑制效应 T 细胞。我们研究了正常和 CTLA-4 缺陷的 Ag 特异性鼠效应 CD4(+) T 细胞的体内反应。我们直接证明了效应 T 细胞受限的 CTLA-4 通过细胞外在的方式抑制 T 细胞反应。共转导实验表明，正常效应 CD4(+) T 细胞上的 CTLA-4 完全消除了其 CTLA-4 缺陷型对应物通常经历的显著扩增。当单独或一起转导时，无论是野生型还是 CTLA-4 缺陷型 T 细胞都不表达 Treg 转录因子 Foxp3。因此，CTLA-4 通过细胞外在机制抑制 T 细胞反应不仅限于 Tregs，而且也是效应 T 细胞的功能。
