Virus-specific CD8+ T cells in the liver:: Armed and ready to kill

Influenza A virus infection of C57BL/6 mice is a well-characterized model for studying CD8(+) T cell-mediated immunity. Analysis of primary and secondary responses showed that the liver is highly enriched for CD8(+) T cells specific for the immunodomiliant N2D(b)NP(366-374) ((DNP366)-N-b) epitope. Functional analysis established that these liver-derived virus-specific CD8(+) T cells are fully competent cytotoxic effectors and IFN-gamma secretors. In addition, flow cytometric analysis of early apoptotic cells showed that these influenza-specific CD8(+) T cells from liver are as viable as those in the spleen, bronchoalveolar lavage, mediastinal lymph nodes, or lung. Moreover, cytokine profiles of the influenza-specific CD8(+) T cells recovered from different sites were consistent with the bronchoalveolar lavage, rather than liver population, being the most susceptible to activation-induced cell death. Importantly, adoptively transferred influenza virus-specific CD8(+) T cells from the liver survived and were readily recalled after virus challenge. Together, these results show clearly that the liver is not a graveyard for influenza virus-specific CD8(+) T cells.