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 (beta(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.
D000818:Animals; D001985:Bronchial Provocation Tests; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*
D018821:CD18 Antigens; D015847:Interleukin-4