Seung-Hyo Lee1, 2, 8, Joseph E Prince1, 3, 7, 8, Muhammad Rais4, Farrah Kheradmand1, 3, Felix Shardonofsky4, Huifang Lu5, Arthur L Beaudet5, C Wayne Smith1, 4, Lynn Soong6
& David B Corry1, 2, 31
Biology of Inflammation Center and Department of Human and Molecular Genetics Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
2
Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
3
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
4
Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
5
Department of Human and Molecular Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
6
Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas 77555, USA.
7
Present address: Southeast Texas Medical Associates, 2929 Calder Avenue, Beaumont, Texas 77702, USA.
8
These authors contributed equally to this work.
Correspondence should be addressed to David B Corry dcorry@bcm.tmc.edu
2 integrin) to TH1 and TH2 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 TH1 immune response, as assessed from draining lymph nodes. In contrast, TH2-dependent allergic lung disease was markedly impaired in mutant mice. In both models, development of TH1 and TH2 cells in spleens was normal, but accumulation of TH2 (not TH1) cells at inflammatory sites was reduced. Thus, CD18 is selectively required for TH2, but not TH1, 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 TH2 cells.
