Non-antigen specific CD8+ T suppressor lymphocytes

Abstract.

The homeostasis of peripheral immune system function is maintained by the activity of regulatory lymphocytes. Among these cells, a subset of CD8+CD28- T suppressor lymphocytes has recently been characterized for the capacity to mediate their effects without antigen restriction. These non-antigen-specific CD8+ T suppressor lymphocytes originate from circulating CD8+CD28- T lymphocytes after stimulation with interleukin-2 and interleukin- 10. CD8+ suppressor cells inhibit both antigen-specific CD4+ T cell proliferation and cellular cytoxicity through secretion of cytokines such as interferon-γ, interleukin-6, and interleukin-10. The function of CD8+ suppressor cells is impaired in patients with systemic lupus erythematosus in relapse as well as in patients with systemic sclerosis with disease progression, suggesting the involvement of CD8+ suppressor cells in the pathogenesis of autoimmune diseases. Interestingly, CD8+ suppressor cells have been found among tumor-infiltrating lymphocytes, which could be related to tumor-induced-immunosuppression. Failure to generate CD8+ suppressor cells from the peripheral blood is frequently observed in HIV-infected patients. It remains to be clarified whether this phenomenon is due to depletion and/or functional impairment of this cell subset or to their compartmentalization in peripheral tissues and immunocompetent organs where they could contribute to the induction of immunodeficiency.