CD4+ T Cells Are Required for the Development of Cytotoxic CD8+ T Cells During Mycobacterium tuberculosis Infection

摘要

The control of acute and chronic Mycobacterium tuberculosis infection is dependent on CD4+ T cells. In a variety of systems CD8+ T cell effector responses are dependent on CD4+ T cell help. The development of CD8+ T cell-mediated immune responses in the absence of CD4+ T cells was investigated 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 CD4+ T cells. Infiltration of CD8+ T cells into infected lungs of CD4?/? or wild-type mice was similar. IFN-γ production by lung CD8+ T cells in CD4?/? and wild-type mice was also comparable, suggesting that emergence of IFN-γ-producing mycobacteria-specific CD8+ T cells in the lungs 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 critical for the development of cytotoxic effector cells, was diminished in the lungs of M. tuberculosis -infected CD4?/? mice. As tuberculosis is frequently associated with HIV infection and a subsequent loss of CD4+ T cells, understanding the interaction between CD4+ and CD8+ T cell subsets during the immune response to M. tuberculosis is imperative for the design of successful vaccination strategies.