Antigen presentation and HLA-DR expression by FK-506-treated human monocytes

The novel macrolide immunosuppressant FK-506 demonstrated superior potency to cyclosporin A (CsA) in the inhibition of purified protein derivative (PPD)-induced human T-cell proliferation. Pulsing of monocytes with PPD for 24 hr in the presence of FK-506 did not impair their capacity to subsequently induced the proliferation of purified autologous T cells. In contrast, FK-506 profoundly inhibited the proliferative response of T cells to antigen-pulsed monocytes. Recombinant IL-2, but not IL-1, partially restored the proliferative response to PPD in the presence of the drug. FK-506 had no effect on basal or rIFN-gamma-induced expression of HLA-DR on monocytic cell line cells. These findings provide the first evidence that FK-506 can profoundly inhibit soluble antigen-induced human T-cell proliferation at concentrations which do not significantly impair the accessory function of mononuclear phagocytes.