Abstract
To understand the integrin requirements of T-helper (TH) effector subsets, we investigated the contribution of CD18 (β2 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.
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Acknowledgements
This work was supported by grants HL69585-01 (to D.B.C.), HL64061-01 (to F.K.) and F32-HL09657-02 (to H.L.) from the National Institutes of Health. We thank J. Xu and Y. Qian for technical assistance, and J.R. Rodgers, B.W. McIntyre and C.M. Ballantyne for helpful discussions.
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Lee, SH., Prince, J., Rais, M. et al. Differential requirement for CD18 in T-helper effector homing. Nat Med 9, 1281–1286 (2003). https://doi.org/10.1038/nm932
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DOI: https://doi.org/10.1038/nm932
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