THYMOCYTES IN THY-1(- -) MICE SHOW AUGMENTED TCR SIGNALING AND IMPAIRED DIFFERENTIATION/

Thy-1, a single variable like immunoglobulin superfamily domain anchor ed in the plasma membrane by a glycosyl phosphaditylinositol tail [1], is a major surface glycoprotein in adult mammalian neurons and rodent thymocytes [2]; the function of Thy-1 has remained enigmatic since it s discovery [3], Studies in vitro have implicated Thy-1 in homotypic a nd heterotypic cell-cell interactions [2,4], Ligation of Thy-1 initiat es transmembrane signaling pathways that lead to diverse physiological outcomes in different cells [2,5-7], In rodents, Thy-1 is highly expr essed on the surface of CD4(+)CD8(+) double-positive immature thymocyt es and downregulated in mature T cells. Here, we report that thymocyte s from Thy-1(-/-) mice [8] had altered cell-cell contacts, and hyperre sponsiveness to T-cell receptor (Tin) triggering as demonstrated by th e heightened activation of p56(lck), phosphorylation of TCR subunits, Ca2+ fluxes and cell proliferation, Thy-1(-/-) thymocytes exhibited im paired maturation from the double positive to single positive stage of thymocyte development, possibly due to inappropriate negative selecti on, and were prone to T lymphomas in aged mice, These observations ind icate that Thy-1 negatively regulates TCR mediated signaling and contr ols activation thresholds during thymocyte differentiation.