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(R)) is a powerful inhibit or of CD4(+) T-cell activation and proliferation in vitro. In this stu dy, immunophenotypic and functional analyses were performed on periphe ral blood mononuclear cells from a total of 30 patients with various a utoimmune disorders before and whilst the patients were receiving syst emic FK506 therapy. The expression of cell surface IL-2R alpha and -be ta on CD4(+) and CD8(+) cells, cytokine message (IL-2, IFN-gamma, IL-4 , IL-10) and the proliferative activity of lymphocytes in response to rIL-2 were examined. Despite plasma levels of FK506 compatible with th e blockade of IL-2 production by stimulated T cells in vitro, cells fr om patients on FK506 treatment cultured ex vivo with either ConA or IL -2 did not differ from normal cells in their expression of cytokine mR NA or their proliferative responses. These data indicate that the pres umed in vivo suppression of T-cell function by FK506 is rapidly revers ible ex vivo. Alternatively/additionally, they suggest that FK506 may mediate its in vivo action primarily by mechanisms other than blockade of T-cell function.