Developmental control of integrin expression regulates Th2 effector homing.
Integrin CD18, a component of the LFA-1 complex that also includes CD11a, is essential for Th2, but not Th1, cell homing, but the explanation for this phenomenon remains obscure. In this study, we investigate the mechanism by which Th2 effector responses require the LFA-1 complex. CD11a-deficient T cells showed normal in vitro differentiation and function. However, Th2 cell-dependent allergic lung disease was markedly reduced in CD11a null mice and wild-type mice given LFA-1 inhibitors, whereas control of infection with Leishmania major, a Th1-dependent response, was enhanced. In both disease models, recruitment of IL-4-, but not IFN-gamma-secreting cells to relevant organs was impaired, as was adhesion of Th2 cells in vitro. These diverse findings were explained by the markedly reduced expression of CD29, an alternate homing integrin, on Th2, but not Th1, cells, which precludes Th2 homing in the absence of CD11a. Thus, murine Th1 and Th2 cells use distinct integrins for homing, suggesting novel opportunities for integrin-based therapeutic intervention in diverse human ailments influenced by Th2 cells.
Lee
Seung-Hyo
SH
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Prince
Joseph E
JE
Rais
Muhammad
M
Kheradmand
Farrah
F
Ballantyne
Christie M
CM
Weitz-Schmidt
Gabriele
G
Smith
C Wayne
CW
Corry
David B
DB
D000485:Allergens / Q000276:immunology; D000818:Animals; D040881:CD11a Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology*; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D018320:Leishmania major / Q000276:immunology; D008171:Lung Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D040881:CD11a Antigen; D019012:Integrin beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1