Human CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T cell activation.
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-gamma 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.
Câmara
Niels Olsen Saraiva
NO
Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Hospital, London, GB.
Sebille
Fabien
F
Lechler
Robert I
RI
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002454:Cell Differentiation; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D016207:Cytokines; D015375:Receptors, Interleukin-2