Regulation of HLA-DR and Invariant Chain Expression by Human Peripheral Blood Mononuclear Cells with Lead, Interferon-γ, or Interleukin-4

Abstract

It has been reported that the expression of major histocompatibility complex (MHC) class II can be regulated by lead (Pb) in murine cells. In both human and mouse, the expression of MHC class II and invariant chain (Ii) can be regulated by cytokines, including interferon-γ (IFN-γ) and interleukin-4 (IL-4). Herein we report that in humans, as with IL-4, Pb enhanced MHC class II antigen DR (HLA-DR) surface expression by monocytes and B cells; Ii surface expression by monocytes and B cells was not affected by Pb while it was enhanced by IL-4. IFN-γ increased HLA-DR and Ii surface expression by monocytes but it decreased HLA-DR and Ii surface expression by B cells. Total cellular HLA-DR expression by peripheral blood mononuclear cells (PBMC) was increased by Pb, IFN-γ, or IL-4. Total cellular Ii (p33 and p35) expression by PBMC was not affected by Pb or IFN-γ while it was increased by IL-4. In PBMC, the steady-state mRNA levels of HLA-DRα and Ii were not affected by Pb; IFN-γ increased HLA-DRα mRNA expression but not Ii; IL-4 increased both mRNA levels of HLA-DRα and Ii. Furthermore, Pb, IFN-γ, or IL-4 significantly increased the total cellular level of HLA-DR:Ii complexes in PBMC while they had no effect on cell surface HLA-DR:Ii complex expression. Overall, these results suggest that,in vitro,Pb, IFN-γ, and IL-4 differentially modulate HLA-DR and Ii expression by human PBMC.