AbstractsBiology & Animal Science

Human regulatory T lymphocytes (Tregs) are a subset of CD4+ T cells that inhibit other T cells by producing TGF-β1, an immunosuppressive cytokine. All T cells produce TGF-β1 as an inactive precursor, but only Tregs are able to activate the cytokine. Activation of TGF-β1 requires binding of the precursor to GARP, a Treg membrane protein. Forced expression of GARP in other T cells (Th) is not sufficient to activate TGF-β1. We thus searched for proteins expressed in Tregs, and not in Th, that interact with GARP and contribute to TGF-β1 activation in these cells. First, we screened a Treg cDNA library by yeast two-hybrid using GARP as bait. We identified LAPTM4B, a membrane protein expressed at higher levels in Tregs than in Th cells. We showed that LAPTM4B is a negative regulator of TGF-β1 production in Tregs but is not involved in TGF-β1 activation. Second, we immunoprecipitated GARP in Treg lysates and identified 7 co-immunoprecipitated proteins by Mass Spectrometry. Four are not involved in TGF-β1 activation, while 3 remain to be tested and may represent Treg proteins that may cooperate with GARP to activate TGF-β1. (BIFA - Sciences biomédicales et pharmaceutiques)  – UCL, 2015