CD8(+) T cell effector mechanisms in resistance to infection

Based on T cell subset depletion studies and the analysis of gene knockout mice, it is evident that CD8(+) T cells contribute to resistance against in tracellular infections with certain viral, protozoan, and bacterial pathoge ns. Although they are known primarily for their capacity to kill infected c ells, CD8(+) T cells elaborate a variety of effector mechanisms with the po tential to defend against infection. Microbes use multiple strategies to ca use infection, and the nature of the pathogen-host interaction may determin e which CD8(+) T cell effector mechanisms are required for immunity. In thi s review, we summarize our current understanding of the effector functions used by CD8(+) T cells in resistance to pathogens. Analyses of mice deficie nt in perforin and/or Fas demonstrate that cytolysis is critical for immuni ty against some, but not all, infections and also reveal the contribution o f cytolysis to the pathogenesis of disease. The role of CD8(+) T cell-deriv ed cytokines in resistance to infection has been analyzed by systemic treat ment with neutralizing antibodies and cytokine gene knockout mice. These st udies are complicated by the fact that few, if any, cytokines are uniquely produced by CD8(+) T cells. Thus, the requirement for CD8(+) T cell-derived cytokines in resistance against most pathogens remains to be defined. Fina lly, recent studies of human CD8(+) T cells reveal the potential for novel effector mechanisms in resistance to infection.