T cells deficient in the tyrosine phosphatase SHP-1 resist suppression by regulatory T cells

Emily R. Mercadante, Ulrike M. Lorenz

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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 Tregmediated 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.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalJournal of Immunology
Volume199
Issue number1
DOIs
StatePublished - Jul 1 2017

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