| First Author | Bold TD | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 5 | Pages | 2530-6 |
| PubMed ID | 22837486 | Mgi Jnum | J:189869 |
| Mgi Id | MGI:5447143 | Doi | 10.4049/jimmunol.1200994 |
| Citation | Bold TD, et al. (2012) CD4+ T cell-dependent IFN-gamma production by CD8+ effector T cells in Mycobacterium tuberculosis infection. J Immunol 189(5):2530-6 |
| abstractText | Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-gamma. However, the precise role and relative contribution of each cell type to in vivo IFN-gamma production are incompletely understood. To identify and quantitate the cells that produce IFN-gamma 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-gamma in the lungs. In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-gamma in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-gamma 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-gamma 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. |
