The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to Mycobacterium tuberculosis in C3H mice.
Both innate and adaptive immunity play an important role in host resistance to Mycobacterium tuberculosis infection. Although several studies have suggested that the major histocompatibility complex (MHC) haplotype affects susceptibility to infection, it remains unclear whether the modulation of T-cell immunity by the MHC locus determines the host's susceptibility to tuberculosis. To determine whether allelic differences in the MHC locus affect the T-cell immune response after M. tuberculosis infection, we infected inbred and H-2 congenic mouse strains by the respiratory route. The H-2 locus has a profound effect on the antigen-specific CD4+-T-cell response after M. tuberculosis infection. CD4+ T cells from infected mice of the H-2(b) haplotype produced more gamma interferon (IFN-gamma) after in vitro stimulation with mycobacterial antigens than mice of the H-2(k) haplotype. A higher level of IFN-gamma was also detected in bronchoalveolar lavage fluid from infected mice of the H-2(b) haplotype. Furthermore, C3.SW-H2(b)/SnJ mice generate and recruit activated T cells to the lung after infection. Despite a robust immune response, C3.SW-H2(b)/SnJ mice succumbed to infection early and were similarly susceptible to infection as other C3H (H-2(k)) substrains. These results suggest that although the MHC haplotype has a profound impact on the T-cell recognition of M. tuberculosis antigens, the susceptibility of C3H mice to infection is MHC independent.
Kamath
Arati B
AB
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Building, Room 516C, One Jimmy Fund Way, Boston, MA 02115, USA.
Alt
Jennifer
J
Debbabi
Hajer
H
Taylor
Chad
C
Behar
Samuel M
SM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000473:pathology
D000942:Antigens, Bacterial; D006183:H-2 Antigens; D007371:Interferon-gamma