Role of ICAM-1 and P-selectin expression in the development and effector function of CD4+CD25+ regulatory T cells

Dynamic regulatory mechanisms prevent autoreactive T cell activation. Upon T cell receptor crosslinking, CD4(+)CD25(+) T regulatory (T-R) cells block both the proliferation and cytokine production of CD4(+)CD25(+) effector cells in an apparent antigen non-specific manner. Within the T-R population, L-selectin (CD62L)(hi) T-R cells have been described as more efficient suppressors of T cell proliferation than CD62L(low) T-R cells. We have previously reported that CD4(+)CD25(+)CD62L(hi) T, cells express elevated levels of two additional adhesion molecules, ICAM-1 (CD54) and P-selectin (CD62P) in comparison to non-T-R cells. In the current study, we investigated the functional contribution of CD54 and CD62P expression to the suppressive phenotype of T-R cells both in vitro and in vivo. While the CD4(+)CD25(+) T-R cell population was demonstrated to be significantly larger in CD62P(-/-) mice than in wild-type C57BL/6 mice, CD62P(-/-) T-R cell function was deficient in vitro, but not in vivo. Interestingly, we detected no deficiencies in T-R cell numbers or effector function in CD54(-/-) mice suggesting that T-R cells may differ from effector CD4(+) T cells in the requirement for CD54 expression within the immunological synapse. Collectively, these findings indicate that CD62P may influence T-R cell differentiation/development and that T-R cell activation occurs independently of CD54 expression. (C) 2003 Published by Elsevier Ltd.