Respiratory virus infections are a major cause of morbidity and mortality worldwide. CD8+ cytotoxic T lymphocytes (CTL) have been shown to play a central role in controlling primary infection and represent an important target for improving current vaccines designed to emphasize cellular responses against this class of viruses. In the current proposal, we take advantage of two well-established models of respiratory virus infections (Sendai virus and influenza virus) to investigate the recall of memory CD8+ T cells. Preliminary data show that substantial numbers of antigen-specific T cells can be found not only in the spleen, but also in the lung tissue and lavage following both Sendai virus and influenza virus infection. Interestingly, memory CD8+ T cells in the lung differ from those observed in the spleen in terms of phenotype and frequency among CD8+ T cells. The underlying hypothesis of the proposal is that memory CD8+ T cells in the lung make a substantial contribution to the rapid recall response during secondary infection. This hypothesis will be tested by (I) characterizing antigen-specific CD8+ memory T cells that persist in the lungs following recovery from respiratory virus infection, and (II) determining the relative contributions of distinct populations of memory cells to the recall response.
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