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SHP‐1 plays a role in both conventional and CD4+CD25+Foxp3+ regulatory T cell function
Author(s) -
Iype Tessy,
Sankarshanan Mohan,
Lorenz Ulrike
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.848.21
Subject(s) - foxp3 , il 2 receptor , microbiology and biotechnology , regulatory t cell , regulator , function (biology) , t cell receptor , in vitro , phenotype , immune system , biology , t cell , immunology , cancer research , chemistry , gene , genetics
While the importance of regulatory T (Treg) cells for immune tolerance has been increasingly appreciated, our mechanistic and molecular understanding of their function is still very limited. We have previously shown that mice lacking the SHP‐1, so‐called motheaten ( me/me ) mice, have increased numbers of Treg cells. SHP‐1 is a well‐recognized negative regulator of TCR‐mediated signaling. We therefore asked whether SHP‐1 also plays a role in Treg function. A comparison of the suppressive capabilities of wild type and me/me Treg cells demonstrated increased suppressive activity of me/me Treg cells in in vitro suppression assays. While this suppression is dependent on stimulation via the TCR, our data indicate that additional factors, which are critical for an effective Treg function, are regulated by SHP‐1. Interestingly when comparing wild type and me/me conventional T cells, we observed that SHP‐1 deficient CD4+CD25‐ T cells are more resistant to Treg‐mediated suppression than wild type T cells, indicating a role for SHP‐1 both in suppression as well as in resistance to suppression. We are currently addressing at the molecular level how SHP‐1 regulates these processes. We expect from these studies to not only better understand the regulatory role of SHP‐1 in conventional and Treg T cells but to also gain further insights into the mechanism of suppression by Treg cells. This work was supported by the NIH grant RO1 AI48672.