CD18 is required for optimal development and function of CD4+ CD25+ T regulatory cells

CD4(+)CD25(+) T regulatory (Treg) cells inhibit immunopathology and autoimmune disease in vivo. CD4(+)CD25(+) Treg cells' capacity to inhibit conventional T cells in vitro is dependent upon cell-cell contact; however, the cell surface molecules mediating this cell:cell contact have not yet been identified. LFA-1 (CD11a/CD18) is an adhesion molecule that plays an established role in T cell-mediated cell contact and in T cell activation. Although expressed at high levels on murine CD4(+)CD25(+) Treg cells, the role of LFA-1 in these cells has not been defined previously. We hypothesized that LYA-1 may play a role in murine CD4(+)CD25(+) Treg function. To evaluate this, we analyzed LFA-1-deficient (CD.18(-/-)) CD4(+)CD25(+) Tcells. We show that CD18(-/-) mice demonstrate a propensity to autoinumunity. Absence of CD18 led to diminished CD4(+)CD25(+) T cell numbers and affected both thymic and peripheral development of these cells. LFA-1-deficient CD4(+) CD25(+) T cells were deficient in mediating suppression in vitro and in mediating protection from colitis induced by the transfer of CD4(+)CD25(-) T cells into lymphopenic hosts. Therefore, we define a crucial role for CD18 in optimal CD4(+)CD25(+) Treg development and function.