Immune Netw.  2014 Dec;14(6):328-332. 10.4110/in.2014.14.6.328.

Evidence for Direct Inhibition of MHC-Restricted Antigen Processing by Dexamethasone

• Im SA
• Gerelchuluun T
• Lee CK

• KMID: 2150823
• DOI: http://doi.org/10.4110/in.2014.14.6.328

Abstract

Dexamethasone (Dex) was shown to inhibit the differentiation, maturation, and antigen-presenting function of dendritic cells (DC) when added during DC generation or maturation stages. Here, we examined the direct effects of Dex on MHC-restricted antigen processing. Macrophages were incubated with microencapsulated ovalbumin (OVA) in the presence of different concentrations of Dex for 2 h, and the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Dex inhibited both class I- and class II-restricted presentation of OVA to T cells; this inhibitory effect on antigen presentation was much more potent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVA peptide SIINFEKL was not blocked by Dex. In addition, short-term treatment of macrophages with Dex had no discernible effects on the phagocytic activity, total expression levels of MHC molecules or co-stimulatory molecules. These results demonstrate that Dex inhibits intracellular processing events of phagocytosed antigens in macrophages.

Keyword

Dexamethasone; MHC-restricted antigen processing; Macrophage

MeSH Terms

Antigen Presentation*
Dendritic Cells
Dexamethasone*
Macrophages
Ovalbumin
Ovum
T-Lymphocytes
Dexamethasone
Ovalbumin

Figure

• 

  Figure 1 Dex inhibits MHC-restricted processing of exogenous antigens. Immature or mature macrophages were incubated with the indicated amounts of Dex for 2 h, followed by addition of OVA-nanospheres (50µg as OVA). After another 2 h incubation at 37℃, the class I and class II MHC-complexed OVA peptide quantities were assessed using OVA-specific CD8 T cell hybridoma B3Z cells (A) and OVA-specific CD4 T cell hybridoma DOBW cells (B), respectively. The indicated amounts of Dex were added to macrophages cultures together with the antigenic OVA-peptide SIINFEKL. The cells were harvested, washed, and the amount of SIINFEKL-H-2Kb complex measured using B3Z cells. Each data point represents the mean±SD of values obtained from three individual experiments.

• 

  Figure 2 Short-term treatment of macrophages with Dex does not affect their phagocytic activity or the expression of cell surface molecules. Immature and mature macrophages were incubated with Dex (10µM) for 2 h, followed by addition of nanospheres containing both OVA and FITC. After an additional 2 h incubation, the cells were washed, harvested, and flow cytometric analysis was performed (A). The shaded histograms represent the phagocytic activity in the presence of Dex, and the thick line histograms in the absence of Dex. The effects of Dex on the expression of class II MHC molecules (I-Ab) and co-stimulatory molecules such as B7-1 were also examined in the macrophages treated with Dex (10 µM) for 4 h (B, C). The shaded histograms represent the expression levels of the cell surface molecules in the presence of Dex, and the thick line histograms in the absence of Dex.

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