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Eur J Immunol. 2007 Jul;37(7):1796-808.

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

Author information

1
Institute of Immunology and Infection Research, University of Edinburgh, Ashworth Laboratories, King's Buildings, Edinburgh, UK.

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.

PMID:
17549732
PMCID:
PMC2699381
DOI:
10.1002/eji.200636661
[Indexed for MEDLINE]
Free PMC Article

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