Regulatory T cells (Tregs) are a specialized subpopulation of T cells that control the immune response and thereby maintain immune system homeostasis and tolerance to self-antigens. Many subsets of CD4+ Tregs have ...Regulatory T cells (Tregs) are a specialized subpopulation of T cells that control the immune response and thereby maintain immune system homeostasis and tolerance to self-antigens. Many subsets of CD4+ Tregs have been identified, including Foxp3~, Trl, Th3, and Foxp3neg iT(R)35 cells. In this study, we identified a new subset of CD4+VEGFR1high Tregs that have immunosuppressive capacity. CD4+VEGFRlhigh T cells, which constitute approximately 1.0% of CD4+ T cells, are hyporesponsive to T-cell antigen receptor stimulation. Surface marker and FoxP3 expression analysis revealed that CD4+VEGFR1high T cells are distinct from known Tregs. CD4+VEGFR1high T cells suppressed the proliferation of CD4+CD25- T cell as efficiently as CD4+CD25high natural Tregs in a contact-independent manner. Furthermore, adoptive transfer of CD4+VEGFR1+ T cells from wild type to RAG-2-deficient C57BL/6 mice inhibited effector T-cell-mediated inflammatory bowel disease. Thus, we report CD4+ VEGFR1high T cells as a novel subset of Tregs that regulate the inflammatory response in the intestinal tract.展开更多
文摘Regulatory T cells (Tregs) are a specialized subpopulation of T cells that control the immune response and thereby maintain immune system homeostasis and tolerance to self-antigens. Many subsets of CD4+ Tregs have been identified, including Foxp3~, Trl, Th3, and Foxp3neg iT(R)35 cells. In this study, we identified a new subset of CD4+VEGFR1high Tregs that have immunosuppressive capacity. CD4+VEGFRlhigh T cells, which constitute approximately 1.0% of CD4+ T cells, are hyporesponsive to T-cell antigen receptor stimulation. Surface marker and FoxP3 expression analysis revealed that CD4+VEGFR1high T cells are distinct from known Tregs. CD4+VEGFR1high T cells suppressed the proliferation of CD4+CD25- T cell as efficiently as CD4+CD25high natural Tregs in a contact-independent manner. Furthermore, adoptive transfer of CD4+VEGFR1+ T cells from wild type to RAG-2-deficient C57BL/6 mice inhibited effector T-cell-mediated inflammatory bowel disease. Thus, we report CD4+ VEGFR1high T cells as a novel subset of Tregs that regulate the inflammatory response in the intestinal tract.