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Developmental Control of Integrin Expression Regulates Th2 Effector Homing¹

Seung-Hyo Lee^2,*,, Joseph E. Prince, Muhammad Rais, Farrah Kheradmand^*,, Christie M. Ballantyne, Gabriele Weitz-Schmidt, C. Wayne Smith^*, and David B. Corry^3,*,

^* Department of Immunology, Department of Medicine, and Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030; and Department of Transplantation and Immunology, Novartis Institutes of Biomedical Research, Novartis Pharma AG, Basel, Switzerland

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--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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants HL69585, HL75243, AI057696, AI070973 (to D.B.C.), and HL 42550 (to C.W.S.) from the National Institutes of Health and the Methodist DeBakey Heart Center (to C.M.B.).

² Current address: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea 305-701.

³ Address correspondence and reprint requests to Dr. David B. Corry, Baylor College of Medicine, One Baylor Plaza, Suite 520B, Houston, TX 77030. E-mail address: dcorry{at}bcm.tmc.edu

⁴ Abbreviations used in this paper: BAL, bronchoalveolar lavage; PLN, popliteal lymph node.