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Regulating T helper cell immunity through antigen responsiveness and calcium entry

Nature Immunology volume 1, pages 402412 (2000) | Download Citation

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Abstract

We evaluated changes in the signaling potentials and proliferative capacity of single antigen–specific T helper (TH) cells during a primary immune response to a protein antigen. At the peak of cellular expansion in vivo all antigen-specific TH cells exhibited a profound block in CD3- and CD4-mediated mobilization of intracellular calcium together with a more global block in T cell receptor–independent capacitative calcium entry (CCE). The proliferative response of these antigen-specific TH cells to anti-CD3, anti-CD28 and IL-2 was also severely blunted. Cross-linking CD69 on a substantial fraction of CD69+ antigen–specific TH cells relieved this block in CCE and restored proliferative capacity in vitro. The CCE rescue operated through a CD69-coupled G protein and required calcium-bound calmodulin and calcineurin. These data reveal critical changes in the responsiveness of antigen-specific TH cells and provide evidence of new mechanisms for the regulation of antigen-specific TH cell development in vivo.

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Acknowledgements

We thank D. Driver, J. Fanelli Panus, J. Mikszta, A. Means, T. Meyer, T. Tedder and M. Krangel for comments on the manuscript; M. Davis and J. Altman for the gift of MCC–I-Ek tetramers; D. Patel (core facility of the Duke Specialized Center of Research in RA) and J. P. Allison for gifts of anti-CD28 and anti-CD3; E. Shevach for the H1.2F3 hybridoma; and the Duke Comprehensive Cancer Center Flow Cytometry Shared Resource and Confocal Microscopy Facility. Supported by a National Institutes of Health grant (AI40215), a post-doctoral fellowship (RRPC) and a Biomedical Sciences Grant (MMW) from the Arthritis Foundation.

Author information

Author notes

    • Gabriel Bikah
    •  & Rebecca R. Pogue-Caley

    These authors contributed equally to this work.

    • Gabriel Bikah

    Present address: GlaxoWellcome, Research and Development, Research Triangle Park, NC 27709, USA.

    • Rebecca R. Pogue-Caley

    Present address: MERIX Bioscience Inc., Research Triangle Park, NC 27709, USA.

Affiliations

  1. Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

    • Gabriel Bikah
    • , Rebecca R. Pogue-Caley
    • , Louise J. McHeyzer-Williams
    •  & Michael G. McHeyzer-Williams

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Correspondence to Michael G. McHeyzer-Williams.

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DOI

https://doi.org/10.1038/80841

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