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CD18 Is Required for Optimal Development and Function of CD4⁺CD25⁺ T Regulatory Cells¹

Marissa Marski^*, Sravanthi Kandula^*, Jerrold R. Turner and Clara Abraham^2,*

^* Department of Medicine and Department of Pathology, University of Chicago, Chicago, IL 60637

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 LFA-1 may play a role in murine CD4⁺CD25⁺ Treg function. To evaluate this, we analyzed LFA-1-deficient (CD18^–/–) CD4⁺CD25⁺ T cells. We show that CD18^–/– mice demonstrate a propensity to autoimmunity. 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.

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