Studies with MHC-deficient knock-out mice reveal impact of both MHC I- and MHC II-dependent T cell responses on Listeria monocytogenes infection.
Mutant mice with a defined genetic defect in the beta 2-microglobulin (beta 2m) or the H2-I-A beta chain, which are virtually devoid of functional CD8 or CD4 alpha beta T cells, respectively, were employed for analyzing immune mechanisms involved in acquired resistance against Listeria monocytogenes. Although the lethal dose of L. monocytogenes was markedly lower for either mouse mutant as compared with their heterozygous control littermates, both beta m -/- and A beta -/- mutants were able to resolve low dose infection. However, in both mouse mutants, the course of disease was exacerbated and clearance was markedly delayed. Vaccine induced immunity against a secondary high dose infection lethal for naive animals was also impaired in beta 2m -/- and A beta -/- mice. However, both mutant mice were still capable of controlling secondary infection. Based on numbers of L. monocytogenes organisms in spleens, beta 2m -/- mutants suffered more dramatically from primary and secondary infection than A beta -/- mice. Ag-induced IFN-gamma secretion was impaired during the early phase of infection in beta 2m -/- mice and at later stages in A beta -/- mice. Modulation of gamma delta T cells by mAb treatment led to significant increase in bacterial load of spleens in both beta 2m -/- and A beta -/- mice. Finally, the development of granulomatous lesions was markedly affected in both mutants. In beta 2m -/- mutants, infiltrative lesions appeared and in A beta -/- mice few inflammatory islets with necrotic centers developed. These data demonstrate the importance of both MHC I- and MHC II-dependent immune mechanisms in acquired resistance to L. monocytogenes and point to the necessity of a coordinated interaction between CD8 and CD4 alpha beta T cells (and probably gamma delta T cells) in anti-L. monocytogenes resistance.
Ladel
C H
CH
Department of Immunology, University of Ulm, Germany.
Flesch
I E
IE
Arnoldi
J
J
Kaufmann
S H
SH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006099:Granuloma / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014611:Vaccination
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma