β2 integrins are of critical importance for leukocyte extravasation through vascular endothelia and for T cell activation. To elucidate the role of β2 integrins in T cell–mediated immune responses, allergic contact dermatitis (ACD), irritant dermatitis, and delayed-type hypersensitivity (DTH) were assessed in mice lacking the β2 integrin subunit, CD18. 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–/–lymph nodes (LNs) contained an abnormal population of CD3–CD44high 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 CD18 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 pathophysiology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene.
Stephan Grabbe, Georg Varga, Stefan Beissert, Meike Steinert, Gunther Pendl, Stephan Seeliger, Wilhelm Bloch, Thorsten Peters, Thomas Schwarz, Cord Sunderkötter, Karin Scharffetter-Kochanek