Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Rheumatology, Allergy & Clinical Immunology, National Hospital Organization Chiba-East National Hospital, Chiba, Japan.
Nat Immunol. 2019 Feb;20(2):218-231. doi: 10.1038/s41590-018-0280-2. Epub 2019 Jan 14.
Regulatory T cells (T cells) can activate multiple suppressive mechanisms in vitro after activation via the T cell antigen receptor, resulting in antigen-independent suppression. However, it remains unclear whether similar pathways operate in vivo. Here we found that antigen-specific T cells activated by dendritic cells (DCs) pulsed with two antigens suppressed conventional naive T cells (T cells) specific for both cognate antigens and non-cognate antigens in vitro but suppressed only T cells specific for cognate antigen in vivo. Antigen-specific T cells formed strong interactions with DCs, resulting in selective inhibition of the binding of T cells to cognate antigen yet allowing bystander T cell access. Strong binding resulted in the removal of the complex of cognate peptide and major histocompatibility complex class II (pMHCII) from the DC surface, reducing the capacity of DCs to present antigen. The enhanced binding of T cells to DCs, coupled with their capacity to deplete pMHCII, represents a novel pathway for T cell-mediated suppression and may be a mechanism by which T cells maintain immune homeostasis.
调节性 T 细胞（T 细胞）在通过 T 细胞抗原受体激活后，在体外可以激活多种抑制机制，从而产生抗原非依赖性抑制。然而，目前尚不清楚在体内是否存在类似的途径。在这里，我们发现，由树突状细胞（DCs）脉冲两种抗原激活的抗原特异性 T 细胞在体外可抑制针对两种同源和非同源抗原的常规幼稚 T 细胞（T 细胞），但在体内仅抑制针对同源抗原的 T 细胞。抗原特异性 T 细胞与 DCs 形成强烈相互作用，从而选择性抑制 T 细胞与同源抗原的结合，但允许旁观者 T 细胞进入。强烈的结合导致同源肽和主要组织相容性复合物 II（pMHCII）复合物从 DC 表面被移除，从而降低了 DC 呈递抗原的能力。T 细胞与 DCs 的结合增强，加上它们耗尽 pMHCII 的能力，代表了 T 细胞介导的抑制的新途径，并且可能是 T 细胞维持免疫平衡的机制。
