期刊
JOURNAL OF IMMUNOLOGY
卷 199, 期 1, 页码 129-137出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1602171
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资金
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [1F31AI110146]
- National Institute of General Medical Sciences [5R01GM064709]
- National Heart, Lung, and Blood Institute [1P01HL120840]
The balance between activation of T cells and their suppression by regulatory T cells (Tregs) is dysregulated in autoimmune diseases and cancer. Autoimmune diseases feature T cells that are resistant to suppression by Tregs, whereas in cancer, T cells are unable to mount antitumor responses due to the Treg-enriched suppressive microenvironment. In this study, we observed that loss of the tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, renders naive CD4(+) and CD8(+) T cells resistant to Treg-mediated suppression in a T cell-intrinsic manner. At the intracellular level, SHP-1 controlled the extent of Akt activation, which has been linked to the induction of T cell resistance to Treg suppression. Finally, under conditions of homeostatic expansion, SHP-1-deficient CD4(+) T cells resisted Treg suppression in vivo. Collectively, these data establish SHP-1 as a critical player in setting the threshold downstream of TCR signaling and identify a novel function of SHP-1 as a regulator of T cell susceptibility to Treg-mediated suppression in vitro and in vivo. Thus, SHP-1 could represent a potential novel immunotherapeutic target to modulate susceptibility of T cells to Treg suppression.
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