Regulation of human cytotoxic T lymphocytes development by the synergistic effect of IL-7 and sCD23.
The present study was undertaken to investigate the interaction of IL-7 and sCD23 on human peripheral blood T cell activation and CTL differentiation. Purified T lymphocytes were stimulated with mitogen plus IL-2 and subcultured for 7 days with IL-7 and/or sCD23. The combination of IL-7 and sCD23 synergistically enhanced the proliferation of both CD4+ and CD8+. T cells. CD8+ T cells, however, were usually more responsive to IL-7 and sCD23. This synergy was observed on both subsets of T cells. Furthermore, these cytokines synergistically augment the CTL activity of CD8+ T cells in both mitogen- and antigen-activated T cells. MAbs anti-IL-2 or anti-IL-2R (CD25) and anti-IL-12 had no effect on T cell proliferation and CD8+ cytotoxic activity induced by IL-7 and sCD23. We analyzed the effect on IFN-gamma induction by CD8+ T cells and found that IL-7 alone was incapable of inducing detectable levels of IFN-gamma production, but together with sCD23 it enhanced the production of IFN-gamma. We also found that IFN-gamma was not required for enhanced CTL activity of CD8+ T cells, because rabbit anti-IFN-gamma did not block the synergistic effects of either cytokine. The data demonstrate that the synergistic stimulatory activity of IL-7 and sCD23 may be of significance in the human CTL development and provide an alternative mechanism of stimulating T cells for use in immunotherapy.
Fratazzi
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Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Avvisati
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Guerriero
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Carini
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D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D006801:Humans; D007111:Immunity, Cellular; D009980:Influenza A virus / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D017455:Receptors, IgE / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*
D007376:Interleukin-2; D015851:Interleukin-7; D017455:Receptors, IgE