Modulation of Major Histocompatibility Complex (MHC) Expression by Interferons and Microbial Agents.

Abstract

In a pure population of rat bone marrow‐derived mononuclear phagocytes (BMMø), the expression of major histocompatibility complex (MHC) molecules and ability to manifest tumoricidal activity were simultaneously studied. Resting BMMø, which express low levels of MHC class II molecules and do not manifest tumoricidal activity, become strongly MHC class II‐positive, and evolve tumoricidal activity within 24 h when incubated with macrophage‐activating lymphokines (MAF) or gamma interferon (IFN‐γ). In contrast, BMMø which were interacted for 24 h with heat‐killed microbial agents (Corynebacterium parvum, Listeria) evolve tumoricidal activity without parallel enhancement of MHC class II expression. IFN‐α,β neither induced tumoricidal activity nor enhanced MHC class II expression. Further experiments have shown that (a) the kinetics of MAF‐ and/or IFN‐γ‐induced amplification of MHC class II expression and of tumoricidal activity are different; (b) enhancement of MHC class II expression by rIFN‐γ is not invariably paralleled by induction of tumoricidal activity; and (c) inhibitors of macrophage tumoricidal activity differ in their ability to affect MHC class II expression. It is concluded from these findings that in a population of pure BMMø, i.e. in the complete absence of lymphocytes, the expression of MHC molecules and induction of tumoricidal activity are independently regulated phenomena; in particular, the enhanced expression of MHC class II molecules is not a prerequisite for induction and/or manifestation of tumoricidal activity by mononuclear phagocytes.