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Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell–dependent B cell responses

Nature Immunology volume 4, pages 765–772 (2003)Cite this article

Abstract

Costimulation through the inducible costimulator (ICOS) and its ligand (ICOSL) is essential for T cell–dependent B cell responses, but the cellular and temporal dynamics underlying its in vivo effects are poorly defined. Here we have shown that Icosl−/− and Icos−/− mice had similar phenotypes and that ICOS-ICOSL costimulation modulated the early but not late phases of IgG1 affinity maturation. Exploiting the adoptive transfer of T or B cells from primed Icosl−/− mice, we provided genetic evidence that costimulation through ICOSL was essential for primary but not secondary helper T cell responses and for the control of both T and B cell activities, resulting in T cell–dependent IgG1 production.

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Figure 1: In vivo ablation of mouse Icosl.
Figure 2: Reduced basal concentrations of IgG1.
Figure 3: Impaired germinal center formation.
Figure 4: Selective defect in TH2 differentiation.
Figure 5: Impaired affinity maturation.
Figure 6: Impaired IgE production and attenuation of allergic airway disease.
Figure 7: Partial rescue of defective IgG1 production by PEG-modified GM-CSF.
Figure 8: Cellular and temporal requirements for ICOS/B7RP-1 costimulation in TCD responses.

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Acknowledgements

We thank T. Horan, M. Zhang, K. Gaida and D. Yanagihara for preparation of the 1B7 monoclonal antibody; G. Kelsoe, M.J. Schlomchik, K. Pfeffer, J. Dewey and A. Hebermann for help with the affinity maturation experiments; M. Bachmann for discussions; M. Saunders for scientific editing; and I. Ng for administrative assistance. This work was supported by the Canadian Institutes of Health Research, Amgen and the Canadian Network for Vaccines and Immunotherapeutics of Cancer and Chronic Viral Diseases.

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  1. Anna Tafuri

    Present address: Hôpital Necker, INSERM U-580, 161, rue de Sèvres, 75743, Paris Cedex, 15, France

Authors and Affiliations

  1. Advanced Medical Discovery Institute, 620 University Avenue, Toronto, M5G 2C1, Ontario, Canada

    Tak W Mak, Arda Shahinian, Andrew Wakeham, Louis-Martin Boucher, Gordon Duncan, Alexandra Ho, Denis Bouchard & Anna Tafuri

  2. Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, M5G 2C1, Ontario, Canada

    Tak W Mak, Arda Shahinian, Andrew Wakeham, Louis-Martin Boucher, Melania Pintilie, Gordon Duncan, Matthew Gronski, Urs Eriksson, Alexandra Ho, Denis Bouchard, Pamela S Ohashi & Anna Tafuri

  3. Amgen, One Amgen Center Drive, Thousand Oaks, 91320-1789, California, USA

    Steve K Yoshinaga & John S Whorisky

  4. Division of Respiratory Disease and Allergy, Centre for Gene Therapeutics, McMaster University, Hamilton, L8N 3Z5, Ontario, Canada

    Beata U Gajewska & Manel Jordana

  5. Department of Pathology, University Hospital Zurich, Zurich, CH-8091, Switzerland

    Bernhard Odermatt

  6. Mount Sinai Hospital, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, M5G 1X5, Ontario, Canada

    Tony Pawson & Friedhelm Bladt

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Mak, T., Shahinian, A., Yoshinaga, S. et al. Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell–dependent B cell responses. Nat Immunol 4, 765–772 (2003). https://doi.org/10.1038/ni947

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