TNFα and IFNγ but Not Perforin Are Critical for CD8 T Cell-Mediated Protection against Pulmonary Yersinia pestis Infection

Septic pneumonias resulting from bacterial infections of the lung are a leading cause of human death worldwide. little is known about the capacity of cd8 t cell-mediated immunity to combat these infections and the types of effector functions that may be most effective. pneumonic plague is an acutely lethal septic pneumonia caused by the gram-negative bacterium yersinia pestis. we recently identified a dominant and protective y. pestis antigen,yope69-77,recognized by cd8 t cells in c57bl/6 mice. here,we use gene-deficient mice,ab-mediated depletion,cell transfers,and bone marrow chimeric mice to investigate the effector functions of yope69-77-specific cd8 t cells and their relative contributions during pulmonary y. pestis infection. we demonstrate that yope69-77-specific cd8 t cells exhibit perforin-dependent cytotoxicity in vivo; however,perforin is dispensable for yope69-77-mediated protection. in contrast,yope69-77-mediated protection is severely impaired when production of tnfα and ifnγ by cd8 t cells is simultaneously ablated. interestingly,tnfα is absolutely required at the time of challenge infection and can be provided by either t cells or non-t cells,whereas ifnγ provided by t cells prior to challenge appears to facilitate the differentiation of optimally protective cd8 t cells. we conclude that cytokine production,not cytotoxicity,is essential for cd8 t cell-mediated control of pulmonary y. pestis infection and we suggest that assays detecting ag-specific tnfα production in addition to antibody titers may be useful correlates of vaccine efficacy against plague and other acutely lethal septic bacterial pneumonias. © 2014 szaba et al.