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Antigen presentation and HLA-DR expression by FK-506-treated human monocytes
J Woo1, D J Propper, A W Thomson
1Department of Pathology, University of Aberdeen, U.K.
Abstract:
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.
Insights
The novel immunosuppressant FK-506 potently inhibits T-cell proliferation induced by purified protein derivative (PPD). FK-506 spares monocyte accessory function, offering a targeted approach to T-cell modulation.
Area of Science:
- Immunology
- Pharmacology
Background:
- Cyclosporin A (CsA) is a standard immunosuppressant.
- Novel macrolide immunosuppressants offer potential therapeutic advantages.
Purpose of the Study:
- To evaluate the potency of FK-506 compared to CsA in inhibiting T-cell proliferation.
- To investigate the effect of FK-506 on monocyte accessory function in T-cell activation.
Main Methods:
- Human T-cell proliferation assays using purified protein derivative (PPD) as antigen.
- Monocyte pulsing experiments with PPD in the presence of FK-506.
- Assessment of cytokine effects (IL-2, IL-1) and HLA-DR expression.
Main Results:
- FK-506 demonstrated superior inhibition of PPD-induced T-cell proliferation compared to CsA.
- FK-506 did not impair monocyte capacity to induce T-cell proliferation.
- FK-506 profoundly inhibited T-cell responses to antigen-pulsed monocytes.
- Recombinant IL-2 partially restored T-cell proliferation in the presence of FK-506.
- FK-506 did not affect HLA-DR expression on monocytic cells.
Conclusions:
- FK-506 is a potent inhibitor of soluble antigen-induced human T-cell proliferation.
- FK-506 preserves essential monocyte accessory functions at effective immunosuppressive concentrations.
- These findings highlight FK-506's potential as a targeted immunosuppressive agent.