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ICOS is critical for T helper cell–mediated lung mucosal inflammatory responses

Nature Immunology volume 2, pages 597–604 (2001)Cite this article

Abstract

We examined the requirement for and cooperation between CD28 and inducible costimulator (ICOS) in effective T helper (TH) cell responses in vivo. We found that both CD28 and ICOS were critical in determining the outcome of an immune response; cytolytic T lymphocyte–associated antigen 4–immunoglobulin (CTLA-4–Ig), ICOS-Ig and/or a neutralizing ICOS monoclonal antibody attenuated T cell expansion, TH2 cytokine production and eosinophilic inflammation. CD28-dependent signaling was essential during priming, whereas ICOS–B7RP-1 regulated TH effector responses, and the up-regulation of chemokine receptors that determine T cell migration. Our data suggests a scenario whereby both molecules regulate the outcome of the immune response but play separate key roles: CD28 primes T cells and ICOS regulates effector responses.

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Figure 1: Characterization of the mAbs to ICOS.
Figure 2: Antigen-induced cytokine production after ICOS neutralization.
Figure 3: ICOS expression during allergic lung inflammation.
Figure 4: ICOS expression in the lung and peribronchiolar lymph nodes during allergic lung inflammation.
Figure 5: OVA-induced BAL leukocyte accumulation and AHR after ICOS neutralization during allergic lung inflammation.
Figure 6: OVA-induced BAL leukocyte accumulation and AHR after ICOS neutralization at different time-points during allergic airway disease.
Figure 7: OVA-induced cytokine production in the BAL fluid after ICOS neutralization during allergic airway disease.
Figure 8: Regulation of chemokine receptor expression in the lymph nodes for ICOS.
Figure 9: OVA-induced IgE production after ICOS neutralization and treatment with CTLA-4–Ig.

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Acknowledgements

We thank K. McDonald for purification of ICOS-Ig, C. Groves for advice on FACS analysis and S. Manning for his contributions to this work.

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Authors and Affiliations

  1. Department of Biology, Inflammation Division, Millennium Pharmaceuticals Inc., 45–75 Sidney St., Cambridge, 02139, MA, USA

    Jose Angel Gonzalo, Jane Tian, Tracy Delaney, Justin Corcoran, James B. Rottman, Jose Lora, Amal Al-garawi, Jose Carlos Gutierrez-Ramos & Anthony J. Coyle

  2. Robert Koch-Institute, Nordufer 20, Berlin, 13353, Germany

    Richard Kroczek

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Correspondence to Anthony J. Coyle.

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Gonzalo, J., Tian, J., Delaney, T. et al. ICOS is critical for T helper cell–mediated lung mucosal inflammatory responses. Nat Immunol 2, 597–604 (2001). https://doi.org/10.1038/89739

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