Mice deficient in CD4 T cells have only transiently diminished levels of IFN-gamma, yet succumb to tuberculosis.
CD4 T cells are important in the protective immune response against tuberculosis. Two mouse models deficient in CD4 T cells were used to examine the mechanism by which these cells participate in protection against Mycobacterium tuberculosis challenge. Transgenic mice deficient in either MHC class II or CD4 molecules demonstrated increased susceptibility to M. tuberculosis, compared with wild-type mice. MHC class II-/- mice were more susceptible than CD4-/- mice, as measured by survival following M. tuberculosis challenge, but the relative resistance of CD4-/- mice did not appear to be due to increased numbers of CD4-8- (double-negative) T cells. Analysis of in vivo IFN-gamma production in the lungs of infected mice revealed that both mutant mouse strains were only transiently impaired in their ability to produce IFN-gamma following infection. At 2 wk postinfection, IFN-gamma production, assessed by RT-PCR and intracellular cytokine staining, in the mutant mice was reduced by >50% compared with that in wild-type mice. However, by 4 wk postinfection, both mutant and wild-type mice had similar levels of IFN-gamma mRNA and protein production. In CD4 T cell-deficient mice, IFN-gamma production was due to CD8 T cells. Thus, the importance of IFN-gamma production by CD4 T cells appears to be early in infection, lending support to the hypothesis that early events in M. tuberculosis infection are crucial determinants of the course of infection.
Caruso
A M
AM
Department of Molecular Genetics and Biochemistry, Central Animal Facilities, University of Pittsburgh School of Medicine, PA 15206, USA.
Serbina
N
N
Klein
E
E
Triebold
K
K
Bloom
B R
BR
Flynn
J L
JL
D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D006099:Granuloma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism*; D007424:Intracellular Fluid / Q000737:chemistry; D008213:Lymphocyte Activation; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000473:pathology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D001500:BCG Vaccine; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D007371:Interferon-gamma