Differential requirement for CD18 in T-helper effector homing

To understand the integrin requirements of T-helper (T H ) effector subsets, we investigated the contribution of CD18 (β 2 integrin) to T H 1 and T H 2 function in vitro and in relevant disease models. CD18-deficient ( Itgb2 −/− ) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2 −/− mice were better able to resolve Leishmania major infection and generated a superior T H 1 immune response, as assessed from draining lymph nodes. In contrast, T H 2-dependent allergic lung disease was markedly impaired in mutant mice. In both models, development of T H 1 and T H 2 cells in spleens was normal, but accumulation of T H 2 (not T H 1) cells at inflammatory sites was reduced. Thus, CD18 is selectively required for T H 2, but not T H 1, homing and has a minimal influence on T-effector development. These findings suggest a new integrin-based therapeutic approach in which the outcomes of diverse diseases may be favorably influenced by altering the homing of T H 2 cells.