Expression and regulation of the HLA-DR antigen on circulating monocytes isolated from patients with rheumatoid...

Using a modified radioimmunoassay, surface labeling of HLA-DR antigens on monocytes revealed reduced densities in patients with active rheumatoid arthritis (RA) (P less than 0.001) and in gold-treated patients (P less than 0.01) versus normal controls. Significant enhancement of DR antigen expression (P = 0.01), with values similar to those of normal monocytes, occurred in patient monocytes preincubated at 37 degrees C overnight, but not in monocytes preincubated at 4 degrees C. This suggested that a temperature-dependent metabolic process is required to enhance antigen expression. The addition of cycloheximide totally inhibited the enhancement of DR antigen density. Incubation of monocytes with exogenous prostaglandin E2 (10(-5)M final concentration) caused a reduction of DR densities on control and on RA monocytes, although this decrease was more marked in the controls. Addition of indomethacin did not affect DR antigen levels on control monocytes, but greatly enhanced the expression of DR antigens on RA monocytes. When HLA-DR antigen levels were estimated in detergent-solubilized membrane preparations, monocytes from patients with active RA demonstrated normal-to-increased densities compared with control monocytes. Thus, although RA monocytes possess a normal ability to synthesize DR molecules, surface expression of these molecules is inhibited; this inhibition may be mediated by prostaglandin E2 acting as a negative suppressive signal.