The role of ICOS in the development of CD4 T cell help and the reactivation of memory T cells

Mahajan, S., Cervera, A., Macleod, M. , Fillatreau, S., Perona-Wright, G. , Meek, S., Smith, A., MacDonald, A. and Gray, D. (2007) The role of ICOS in the development of CD4 T cell help and the reactivation of memory T cells. European Journal of Immunology, 37(7), pp. 1796-1808. (doi: 10.1002/eji.200636661) (PMID:17549732) (PMCID:PMC2699381)

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Abstract

We have addressed the role of the inducible costimulator (ICOS) in the development of T cell help for B cells and in the generation, survival and reactivation of memory CD4 T cells and B cells. We find that while T cell help for all antibody isotypes (including IgG2c) is impaired in ICOS knockout (ICOS-KO) mice, the IFN-γ response is little affected, indicating a defect in helper function that is unrelated to cytokine production. In addition, the ICOS-negative T cells do not accumulate in B cell follicles. Secondary (memory), but not primary, clonal proliferation of antigen-specific B cells is impaired in ICOS-KO mice, as is the generation of secondary antibody-secreting cells. Analysis of endogenous CD4 memory cells in ICOS-KO mice, using MHC class II tetramers, reveals normal primary clonal expansion, formation of memory clones and long-term (10 wk) survival of memory cells, but defective expansion upon reactivation in vivo. The data point to a role of ICOS in supporting secondary, memory and effector T cell responses, possibly by influencing cell survival. The data also highlight differences in ICOS dependency of endogenous T cell proliferation in vivo compared to that of adoptively transferred TCR-transgenic T cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macleod, Dr Megan and Perona-Wright, Dr Georgia
Authors: Mahajan, S., Cervera, A., Macleod, M., Fillatreau, S., Perona-Wright, G., Meek, S., Smith, A., MacDonald, A., and Gray, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Journal Abbr.:Eur. J. Immunol.
Publisher:Wiley VCH-Verlag
ISSN:0014-2980
ISSN (Online):1521-4141
Published Online:04 June 2007
Copyright Holders:Copyright © 2007 Wiley Online Library
First Published:First published in European Journal of Immunology 37(7):1796-1808
Publisher Policy:Reproduced in accordance with the Online Open policy of the publisher

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