INTERFERON-GAMMA AND INTERLEUKIN-10 HAVE CROSS-REGULATORY ROLES IN MODULATING THE CLASS-I AND CLASS-II MHC-MEDIATED PRESENTATION OF EPITOPES OF LISTERIA-MONOCYTOGENES BY INFECTED MACROPHAGES

IFN-gamma is an important cytokine in resistance to infection with Lis teria monocytogenes, and interleukin 10 is known to exacerbate infecti on with Listeria and other intracellular pathogens. We examined the ef fects of these cytokines on antigen presentation by macrophages infect ed with live Listeria. Listeriolysin O, a hemolysin secreted by Lister ia, is an immunodominant antigen presented by both class I and class I I MHC on infected cells. Thioglycollate-elicited macrophages were pret reated with exogenous IFN-gamma, IL-10, or both cytokines overnight, i nfected with bacteria, and then fixed. Epitope-specific, MHC-restricte d, T cell hybridomas were then added to detect the presentation of the class I or class II ligand. We found that IFN-gamma enhanced the pres entation of both the class I and class II epitopes and IL-10 strongly inhibited the presentation of both ligands. The degree of inhibition o f presentation caused by IL-10 was dose dependent. IL-10 was also able to inhibit the presentation of exogenously added class II-binding pep tide but had a less dramatic effect on the presentation of the added c lass I-binding polypeptide epitope. Flow cytometric analysis of expres sion of class I and class II on treated macrophaes demonstrated that t he inhibitory effect of IL-10 on antigen presentation was not due to s ignificant downregulation of MHC expression. This loss of antigen pres entation was also not due to downregulation of the costimulatory molec ule, B7-2. We have found that IFN-gamma and IL-10 have opposing immuno regulatory effects on the presentation of antigens derived from an int racellular pathogen and that the class I vs. class II-mediated present ation of antigens is differentially regulated by IL-10.