Human CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T cell activation

Authors

  • Niels Olsen Saraiva Câmara,

    1. Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Hospital, London, GB
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  • Fabien Sebille,

    1. Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Hospital, London, GB
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  • Robert I. Lechler

    Corresponding author
    1. Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Hospital, London, GB
    • Department of Immunology, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, GB Fax: +44-208-3832788
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Abstract

Amongst the many types of regulatory cells that have been described during the past few years, the spontaneously occurring population that is characterized by co-expression of CD4 and CD25 appears to play a key role in the prevention of autoimmunity and the maintenance of transplantation tolerance. In this study we have examined the ability of CD4+CD25+ T cells to regulate human CD8+ T cells, and the behavior of CD8+ T cells following activation in the presence of regulatory CD4+CD25+ T cells. The experiments described here demonstrate that human CD4+CD25+ T cells cause pronounced and sustained inhibition of CD8+ T cell proliferation in response to polyclonal and allogeneic stimulation. The regulation of CD8+ T cell activation was cell contact-dependent and included inhibition of perforin, granzyme B and IFN-γ cytokine production at the transcriptional level and impaired cytotoxicity. The regulated CD8+ T cell population showed sustained hyporesponsiveness and refractoriness to exogenous IL-2. These data provide insights into the short- and long-term effects of CD4+CD25+ T cells on CD8+ T cells that could be of considerable value in optimizing vaccination against tumor and viral antigens.

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