β2 integrins are required for skin homing of primed T cells but not for priming naive T cells

beta(2) integrins are of critical importance for leukocyte extravasation through vascular endothelia. and for T cell activation. To elucidate the role Of 2 integrins in T cell-mediated immune responses, allergic contact dermatitis (ACD), irritant dermatitis, and delayed-type hypersensitivity (DTH) were assessed in mice lacking the beta(2) integrin subunit, CD 18. ACD and DTH responses, but not edema formation,were severely suppressed in CD18(-/-) mice. Extravasation of CD18(-/-) T cells into eczematous skin lesions was greatly impaired, whereas migration of Langerhans cell precursors and dendritic cells was normal in CD18(-/-)mice. CD18(-/-)Iymph nodes (LNs) contained an abnormal population of CD3-CD44(high) lymphocytes and showed evidence of widespread T cell activation. T cells from regional LNs of sensitized CD18(-/-) mice proliferated in response to hapten challenge, and subcutaneous injection of sensitized syngeneic LN cells directly into ears of hapten-challenged naive recipients restored the defective ACD in CD18(-/-) mice, suggesting that CD 18 is not required for priming of naive T cells but is indispensable for T cell extravasation. Thus, a dysfunction of T cells, in addition to granulocytes, may contribute to the pathophysicology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene.