Differential requirement for CD18 in T-helper effector homing

Abstract

To understand the integrin requirements of T-helper (T_H) effector subsets, we investigated the contribution of CD18 (β₂ integrin) to T_H1 and T_H2 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_H1 immune response, as assessed from draining lymph nodes. In contrast, T_H2-dependent allergic lung disease was markedly impaired in mutant mice. In both models, development of T_H1 and T_H2 cells in spleens was normal, but accumulation of T_H2 (not T_H1) cells at inflammatory sites was reduced. Thus, CD18 is selectively required for T_H2, but not T_H1, 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_H2 cells.