Mechanism of action of cyclosporin A in vivo. I. Cyclosporin A fails to inhibit T lymphocyte activation in response to alloantigens
Kroczek, R.A.; Black, C.D.; Barbet, J.; Shevach, E.M.
Journal of Immunology 139(11): 3597-3603
1987
ISSN/ISBN: 0022-1767 PMID: 3119712 Document Number: 304201
Although cyclosporin A (Cy A) has been widely used clinically as a potent suppressor of organ allograft rejection and has been shown to block T lymphocyte activation in vitro by inhibiting the generation of interleukin 2 (IL-2) and other lymphokines, little direct evidence is available to support the view that the immunosuppressive effects of Cy A in vivo are mediated by a similar inhibition of the autocrine lymphokine cascade. We have used a quantitative assay for the assessment of the role of the IL-2 /IL-2 receptor system in the activation of the draining popliteal lymph node population after the injection of allogeneic cells in the footpad to define the effects of Cy A on the early events of lymphocyte activation in vivo and to compare them with the effects of Cy A on lymphocyte activation in vitro. The administration of Cy A in vivo had no effect on alloantigen-induced increases in cell size. percentage of cells expressing the IL-2 receptor, the spontaneous or IL-2-driven proliferation of freshly explanted cells, or the induction of cytotoxic T lymphocyte activity. These findings raise major questions about the mechanisms of action of Cy A in vivo and suggest that more experimentation is required to probe the mechanisms of Cy A-induced suppression of the response to allografts.