| First Author | Szaba FM | Year | 2014 |
| Journal | PLoS Pathog | Volume | 10 |
| Issue | 5 | Pages | e1004142 |
| PubMed ID | 24854422 | Mgi Jnum | J:246458 |
| Mgi Id | MGI:5915130 | Doi | 10.1371/journal.ppat.1004142 |
| Citation | Szaba FM, et al. (2014) TNFalpha and IFNgamma but not perforin are critical for CD8 T cell-mediated protection against pulmonary Yersinia pestis infection. PLoS Pathog 10(5):e1004142 |
| abstractText | 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 TNFalpha and IFNgamma by CD8 T cells is simultaneously ablated. Interestingly, TNFalpha is absolutely required at the time of challenge infection and can be provided by either T cells or non-T cells, whereas IFNgamma 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 TNFalpha production in addition to antibody titers may be useful correlates of vaccine efficacy against plague and other acutely lethal septic bacterial pneumonias. |
