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

Abstract

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 Rpopulation, l-selectin (CD62L) hiT Rcells have been described as more efficient suppressors of T cell proliferation than CD62L lowT Rcells. We have previously reported that CD4 +CD25 +CD62L hiT Rcells express elevated levels of two additional adhesion molecules, ICAM-1 (CD54) and P-selectin (CD62P) in comparison to non-T Rcells. In the current study, we investigated the functional contribution of CD54 and CD62P expression to the suppressive phenotype of T Rcells both in vitro and in vivo. While the CD4 +CD25 +T Rcell population was demonstrated to be significantly larger in CD62P −/−mice than in wild-type C57BL/6 mice, CD62P −/−T Rcell function was deficient in vitro, but not in vivo. Interestingly, we detected no deficiencies in T Rcell numbers or effector function in CD54 −/−mice suggesting that T Rcells 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 Rcell differentiation/development and that T Rcell activation occurs independently of CD54 expression.