T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5′-adenosine monophosphate to adenosine

被引:333
作者
Kobie, James J.
Shah, Pranav R.
Yang, Li
Rebhahn, Jonathan A.
Fowell, Deborah J.
Mosmann, Tim R.
机构
[1] Univ Rochester, Med Ctr, David H Smith Ctr Vaccine Biol & Immunol, Rochester, NY 14642 USA
[2] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
关键词
D O I
10.4049/jimmunol.177.10.6780
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD73 (5'-ectonucleotidase) is expressed by two distinct mouse CD4 T cell populations: CD25(+) (FoxP3(+)) T regulatory (Treg) cells that suppress T cell proliferation but do not secrete IL-2, and CD25(-) uncommitted primed precursor Th (Thpp) cells that secrete IL-2 but do not suppress in standard Treg suppressor assays. CD73 on both Treg and Thpp cells converted extracellular 5'-AMP to adenosine. Adenosine suppressed proliferation and cytokine secretion of Th1 and Th2 effector cells, even when target cells were activated by anti-CD3 and anti-CD28. This represents, an additional suppressive mechanism of Treg cells and a previously unrecognized suppressive activity of Thpp cells. Infiltration of either Treg or Thpp cells at inflammatory sites could potentially convert 5'-AMP generated by neutrophils or dying cells into the anti-inflammatory mediator adenosine, thus dampening excessive immune reactions.
引用
收藏
页码:6780 / 6786
页数:7
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