Blood lymphocytes of autoimmune disease patients receiving FK506 exhibit normal ex vivo cytokine gene expression and proliferative responses

It is well recognized that FK506 (Tacrolimus®) is a powerful inhibitor of CD4+ T-cell activation and proliferation in vitro. In this study, immunophenotypic and functional analyses were performed on peripheral blood mononuclear cells from a total of 30 patients with various autoimmune disorders before and whilst the patients were receiving systemic FK506 therapy. The expression of cell surface IL-2Rα and -β on CD4+ and CD8+ cells, cytokine message (IL-2, IFN-γ, IL-4, IL-10) and the proliferative activity of lymphocytes in response to rIL-2 were examined. Despite plasma levels of FK506 compatible with the blockade of IL-2 production by stimulated T cells in vitro, cells from patients on FK506 treatment cultured ex vivo with either ConA or IL-2 did not differ from normal cells in their expression of cytokine mRNA or their proliferative responses. These data indicate that the presumed in vivo suppression of T-cell function by FK506 is rapidly reversible ex vivo. Alternatively/additionally, they suggest that FK506 may mediate its in vivo action primarily by mechanisms other than blockade of T-cell function.