CD4(+) T cells are required for the development of cytotoxic CD8(+) T cells during Mycobacterium tuberculosis infection

The control of acute and chronic Mycobacterium tuberculosis infection is de pendent on CD4(+) T cells. In a variety of systems CD8(+) T cell effector r esponses are dependent on CD4(+) T cell help. The development of CD8(+) T c ell-mediated immune responses in the absence of CD4(+) T cells was investig ated in a murine model of acute tuberculosis. In vitro and in vivo, priming of mycobacteria-specific CD8(+) T cells was unaffected by the absence of C D4(+) T cells. Infiltration of CD8(+) T cells into infected lungs of CD4(-/ -) or wild-type mice was similar. IFN-gamma production by lung CD8(+) T cel ls in CD4(-/-) and wild-type mice was also comparable, suggesting that emer gence of IFN-gamma -producing mycobacteria-specific CD8(+) T cells in the l ungs was independent of CD4(+) T cell help. In contrast, cytotoxic activity of CD8(+) T cells from lungs of M. tuberculosis-infected mice was impaired in CD4(-/-) mice. Expression of mRNA for IL-2 and IL-15, cytokines critica l for the development of cytotoxic effector cells, was diminished in the lu ngs of M. tuberculosis-infected CD4(-/-) mice. As tuberculosis is frequentl y associated with HIV infection and a subsequent loss of CD4(+) T cells, un derstanding the interaction between CD4(+) and CD8(+) T cell subsets during the immune response to M. tuberculosis is imperative for the design of suc cessful vaccination strategies.