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 Listeria monocytogenes, and interleukin 10 is known to exacerbate infection with Listeria and other intracellular pathogens. We examined the effects of these cytokines on antigen presentation by macrophages infected with live Listeria. Listeriolysin O, a hemolysin secreted by Listeria, is an immunodominant antigen presented by both class I and class II MHC on infected cells. Thioglycollate-elicited macrophages were pretreated with exogenous IFN-gamma, IL-10, or both cytokines overnight, infected with bacteria, and then fixed. Epitope-specific, MHC-restricted, 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 presentation of both the class I and class II epitopes and IL-10 strongly inhibited the presentation of both ligands. The degree of inhibition of presentation caused by IL-10 was dose dependent. IL-10 was also able to inhibit the presentation of exogenously added class II-binding peptide but had a less dramatic effect on the presentation of the added class I-binding polypeptide epitope. Flow cytometric analysis of expression of class I and class II on treated macrophages demonstrated that the inhibitory effect of IL-10 on antigen presentation was not due to significant downregulation of MHC expression. This loss of antigen presentation was also not due to downregulation of the costimulatory molecule, B7-2. We have found that IFN-gamma and IL-10 have opposing immunoregulatory effects on the presentation of antigens derived from an intracellular pathogen and that the class I vs. class II-mediated presentation of antigens is differentially regulated by IL-10.
Hiltbold
E M
EM
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ziegler
H K
HK
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000939:Epitopes; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000188:drug therapy / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D000942:Antigens, Bacterial; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma