Modulation of major histocompatibility complex (MHC) expression by interferons and microbial agents. Independent regulation of MHC class II expression and induction of tumoricidal activity in bone marrow-derived mononuclear phagocytes.
In a pure population of rat bone marrow-derived mononuclear phagocytes (BMM phi), the expression of major histocompatibility complex (MHC) molecules and ability to manifest tumoricidal activity were simultaneously studied. Resting BMM phi, 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-gamma). In contrast, BMM phi 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-alpha,beta neither induced tumoricidal activity nor enhanced MHC class II expression. Further experiments have shown that (a) the kinetics of MAF- and/or IFN-gamma-induced amplification of MHC class II expression and of tumoricidal activity are different; (b) enhancement of MHC class II expression by rIFN-gamma 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 BMM phi, 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.
Keller
R
R
Institute for Immunology and Virology, University of Zurich, Switzerland.
Joller
P
P
Keist
R
R
Binz
H
H
van der Meide
P H
PH
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells; D003602:Cytotoxicity, Immunologic; D006649:Histocompatibility Antigens / Q000032:analysis; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D008089:Listeria monocytogenes / Q000276:immunology* / Q000502:physiology; D008222:Lymphokines / Q000378:metabolism* / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000276:immunology; D008297:Male; D011425:Propionibacterium acnes / Q000276:immunology* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D006649:Histocompatibility Antigens; D008222:Lymphokines; D016215:Macrophage-Activating Factors; C038353:histocompatibility antigens RT, rat; D007372:Interferons