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 tubercu losis. Two mouse models deficient in CD4 T cells were used to examine the m echanism by which these cells participate in protection against Mycobacteri um 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 t han CD4(-/-) mice, as measured by survival following M, tuberculosis challe nge, 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 pr oduce IFN-gamma following infection. At 2 wk postinfection, IFN-gamma produ ction, assessed by RT-PCR and intracellular cytokine staining, in the mutan t mice was reduced by >50% compared with that in wild-type mice. However, b y 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-ga mma production was due to CD8 T cells. Thus, the importance of IFN-gamma pr oduction by CD4 T cells appears to be early in infection, lending support t o the hypothesis that early events in M. tuberculosis infection are crucial determinants of the course of infection.