title: Human CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T cell activation.
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-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.
authors.affiliation: Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Hospital, London, GB.
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
authors.forename: Fabien
authors.initials: F
authors.lastname: Sebille
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: 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
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2