title: H-2 alleles contribute to antigen 85-specific interferon-gamma responses during Mycobacterium tuberculosis infection.
abstract: The in vitro immune responses to mycobacterial antigens have been linked to the H-2 loci in mice. We evaluated in vitro and in vivo immune responses during early Mycobacterium tuberculosis (M.tb) pulmonary infection of C57BL/6 (H-2(b)), C57BL/6 (H-2(k)), CBA/J (H-2(k)), and C3H/HeJ (H-2(k)) mice to determine H-2(k)-dependent and -independent effects. H-2(k)-dependent effects included delayed and diminished Ag85-specific Th1 cell priming, a reduced frequency of Ag85-specific IFN-γ producing cells, reduced IFN-γ protein in vivo, and increased M.tb lung burden as demonstrated by C57BL/6 H-2(k) mice vs. C57BL/6 mice. H-2(k)-independent factors controlled the amount of Ag85-specific IFN-γ produced by each cell, T cell numbers, granuloma size, and lymphocytic infiltrates in the lungs. Overall, these results suggest that an H-2(k)-dependent suboptimal generation of Ag85-specific cells impairs control of early M.tb growth in the lungs. H-2(k)-independent factors influence the potency of IFN-γ producing cells and immune cell trafficking during pulmonary M.tb infection.
authors.affiliation: Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Beamer
authors.forename: Joshua
authors.initials: J
authors.lastname: Cyktor
authors.forename: Bridget
authors.initials: B
authors.lastname: Carruthers
authors.forename: Joanne
authors.initials: J
authors.lastname: Turner
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000483:Alleles; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D054884:Host-Pathogen Interactions / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D006183:H-2 Antigens; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis