Evidence for Direct Inhibition of MHC-Restricted Antigen Processing by Dexamethasone
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Dexamethasone (Dex) was shown to inhibit the differentiation,maturation, and antigen-presenting function ofdendritic cells (DC) when added during DC generation ormaturation stages. Here, we examined the direct effects ofDex on MHC-restricted antigen processing. Macrophageswere incubated with microencapsulated ovalbumin (OVA) inthe presence of different concentrations of Dex for 2 h, andthe efficacy of OVA peptide presentation was evaluated usingOVA-specific CD8 and CD4 T cells. Dex inhibited bothclass I- and class II-restricted presentation of OVA to T cells;this inhibitory effect on antigen presentation was much morepotent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVApeptide SIINFEKL was not blocked by Dex. In addition,short-term treatment of macrophages with Dex had no discernibleeffects on the phagocytic activity, total expressionlevels of MHC molecules or co-stimulatory molecules. Theseresults demonstrate that Dex inhibits intracellular processingevents of phagocytosed antigens in macrophages
Abstract
Dexamethasone (Dex) was shown to inhibit the differentiation,maturation, and antigen-presenting function ofdendritic cells (DC) when added during DC generation ormaturation stages. Here, we examined the direct effects ofDex on MHC-restricted antigen processing. Macrophageswere incubated with microencapsulated ovalbumin (OVA) inthe presence of different concentrations of Dex for 2 h, andthe efficacy of OVA peptide presentation was evaluated usingOVA-specific CD8 and CD4 T cells. Dex inhibited bothclass I- and class II-restricted presentation of OVA to T cells;this inhibitory effect on antigen presentation was much morepotent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVApeptide SIINFEKL was not blocked by Dex. In addition,short-term treatment of macrophages with Dex had no discernibleeffects on the phagocytic activity, total expressionlevels of MHC molecules or co-stimulatory molecules. Theseresults demonstrate that Dex inhibits intracellular processingevents of phagocytosed antigens in macrophages
참고문헌 (25)
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