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CD4+ T cell-dependent IFN-? production by CD8+ effector T cells in Mycobacterium tuberculosis infection.


ABSTRACT: Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-?. However, the precise role and relative contribution of each cell type to in vivo IFN-? production are incompletely understood. To identify and quantitate the cells that produce IFN-? at the site of Mycobacterium tuberculosis infection in mice, we used direct intracellular cytokine staining ex vivo without restimulation. We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo, and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-? in the lungs. In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-? in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-? production by CD8+ effector cells. Accordingly, when infected mice were treated i.v. with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells but independent of IFN-g responsiveness of the CD8+ cells. These data provide evidence that CD4+ cell deficiency impairs IFN-? production by CD8+ effector cells and that ongoing cross-talk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. Conversely, defects in these interactions may contribute to susceptibility to tuberculosis and other infections.

PROVIDER: S-EPMC3424308 | BioStudies |

REPOSITORIES: biostudies

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