REGULATION OF HLA-DR AND INVARIANT CHAIN EXPRESSION BY HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS WITH LEAD, INTERFERON-GAMMA, OR INTERLEUKIN-4

It has been reported that the expression of major histocompatibility c omplex (MHC) class II can be regulated by lead (Pb) in murine cells. I n both human and mouse, the expression of MHC class II and invariant c hain (Ii) can be regulated by cytokines, including interferon-gamma (I FN-gamma) and interleukin-4 (IL-4). Herein we report that in humans, a s with IL-4, Pb enhanced MHC class II antigen DR (HLA-DR) surface expr ession by monocytes and B cells; Ii surface expression by monocytes an d B cells was not affected by Pb while it was enhanced by IL-4. IFN-ga mma increased HLA-DR and Ii surface expression by monocytes but it dec reased HLA-DR and Ii surface expression by B cells. Total cellular HLA -DR expression by peripheral blood mononuclear cells (PBMC) was increa sed by Pb, IFN-gamma, or IL-4, Total cellular Ii (p33 and p35) express ion by PBMC was not affected by Pb or IFN-gamma while it was increased by IL-4. In PBMC, the steady-state mRNA levels of HLA-DR alpha and Ii were not affected by Pb; IFN-gamma increased HLA-DR alpha mRNA expres sion but not Ii; IL-4 increased both mRNA levels of HLA-DR alpha and I i, Furthermore, Pb, IFN-gamma or IL-4 significantly increased the tota l cellular level of HLA-DR:Ii complexes in PBMC while they had no effe ct on cell surface HLA-DR:Ii complex expression. Overall, these result s suggest that, in vitro, Pb, IFN-gamma, and IL-4 differentially modul ate HLA-DR and Ii expression by human PBMC. (C) 1996 Academic Press, I nc.