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_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.