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The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE

Nature Immunology volume 2, pages 605–611 (2001)Cite this article

Abstract

The inducible costimulatory molecule (ICOS) is expressed on activated T cells and participates in a variety of important immunoregulatory functions. After the induction of experimental allergic encephalomyelitis in SJL mice with proteolipid protein (PLP), brain ICOS mRNA and protein were up-regulated on infiltrating CD3+ T cells before disease onset. ICOS blockade during the efferent immune response (9–20 days after immunization) abrogated disease, but blockade during antigen priming (1–10 days after immunization) exacerbated disease. Upon culture with PLP and compared with immunized controls, splenocytes produced either decreased interferon-γ (IFN-γ, in efferent blockade) or excessive IFN-γ (in priming blockade). PLP-specific immunoglobulin G1 was decreased in animals treated with anti-ICOS during antigen priming, but not in other groups.

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Figure 1: Brain infiltration with CD3+ ICOS+ T cells correlates with onset of clinical symptoms
Figure 2: Clinical symptoms in animals treated with anti-ICOS at various stages of the immune response.
Figure 3: ICOS blockade during antigen priming enhances brain leukocyte infiltration on day 14; blockade during the efferent immune response inhibits CNS inflammation.
Figure 4: RPA of brain chemokine, chemokine receptor and cytokine mRNA expression.
Figure 5: Splenocyte IFN-γ production and proliferation upon exposure to recall antigen on day 12 after immunization.
Figure 6: Plasma PLP-specific IgG1 is decreased in mice treated with anti-ICOS during antigen priming.

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Acknowledgements

We thank W. Hancock and C. Horvath for critical review of this manuscript and K. McDonald for antibody production and purification.

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  1. Millennium Pharmaceuticals, 640 Memorial Drive, Cambridge, 02139, MA, USA

    James B. Rottman, Tammy Smith, James R. Tonra, Kenneth Ganley, Troy Bloom, Robert Silva, Barbara Pierce, Jose-Carlos Gutierrez-Ramos, Engin Özkaynak & Anthony J. Coyle

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Correspondence to James B. Rottman.

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Rottman, J., Smith, T., Tonra, J. et al. The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE. Nat Immunol 2, 605–611 (2001). https://doi.org/10.1038/89750

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