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

TitleThe role of ICOS in the development of CD4 T cell help and the reactivation of memory T cells.
Publication TypeJournal Article
Year of Publication2007
AuthorsMahajan S, Cervera A, MacLeod M, Fillatreau S, Perona-Wright G, Meek S, Smith AG, MacDonald A, Gray D
JournalEur J Immunol
Volume37
Issue7
Pagination1796-808
Date Published2007 Jul
ISSN0014-2980
KeywordsAdoptive Transfer, Animals, Antigens, Differentiation, T-Lymphocyte, B-Lymphocytes, CD4-Positive T-Lymphocytes, Cell Differentiation, Cytokines, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunoglobulin Class Switching, Immunohistochemistry, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lymphocyte Activation, Mice, Mice, Knockout
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-gamma 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.

DOI10.1002/eji.200636661
Alternate JournalEur. J. Immunol.
PubMed ID17549732
PubMed Central IDPMC2699381
Grant ListG120/822 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom