Fig. 2.

Mechanisms of T cell-mediated protection. CD8⁺ T cells differentiate in the infection with rickettsiae to cytotoxic T cells that induce apoptosis in infected cells via the release of perforin and granzymes. In addition, CD8⁺ T cells produce IFNγ and TNFα. These cytokines induce the production of NO by MΦ and other cells and, thus, enable bacterial killing. The release of cytokines by CD8⁺ T cells is sufficient for protection at least in the infection with some rickettsial species such as R. typhi where the cytotoxic activity is not essential for bacterial defense (a). CD4⁺ T cells usually differentiate into T_H1 cells that produce IFNγ and TNFα in the infection with rickettsiae. T_H1 cells are protective by the induction of NO and bacterial killing by MΦ and other cells (b). In the absence of IFNγ, CD4⁺ T cells develop into T_H17 cells in the infection with rickettsiae. These cells release IL-17A, IL-22 and TNFα. IL-17A and TNFα synergistically induce the production of NO und ROS by MΦ and other cells. In addition, these cytokines induce the release of proinflammatory cytokines. IL-17A further induces the production of chemokines, leading to the recruitment of neutrophils that contribute to local inflammation. IL-22 does not act on immune cells but various tissue cells. IL-22 induces the release of antimicrobial peptides and other factors and can contribute in this way to bacterial elimination. At least in the infection with R. typhi T_H17 cells can be protective. However, the combined release of TNFα and IL-17A is non-beneficial and exerts pathological effects. Inhibition of either TNFα or IL-17A in this situation renders T_H17 cells as protective as T_H1 cells (c)