Regulation and function of T1/ST2 expression on CD4(+) T cells: Induction of type 2 cytokine production by T1/ST2 cross-linking

wThe orphan receptor T1/ST2 a member of the IL-1R family, is preferentially expressed on the surface of murine Th2 cells. in this study, we analyzed t he kinetics and function of T1/ST2 expression on Th2 cells in vitro. Wherea s naive CD4+ cells did not express T1/ST2, most CD4+ cells became T1/ST2+ u pon repeated antigenic stimulation under Th2-polarizing conditions. Flow cy tometric analyses revealed that the kinetics of T1/ST2 expression on Th2 ce lls was delayed compared with the kinetics of type 2 cytokine production. E xogenous IL-6, IL-5, IL-1, and TNF-alpha enhanced the expression of T1/ST2 on Th2 cells, and IL-6 was by far most effective in this regard. However, t he expression of T1/ST2 did not depend on the presence of IL-6 and was also detected in IL-6-deficient mice, Most important, cross-linking of T1/ST2 p rovided a costimulatory signal for Th2 but not Th1 cells and directly induc ed proliferation and type 2 cytokine production. Thus, T1/ST2 is not only a Th2 cell marker but also plays an important role in the activation of Th2 cells.