Long-term persistence and reactivation of T cell memory in the lung of mice infected with respiratory syncytial virus

Abstract

In mice acutely infected with respiratory syncytial virus (RSV), more than 20% of pulmonary CD8+ T cells, but only 2-3% of CD8+ T cells in the draining lymph node secreted interferon-γ in response to a single peptide. Surprisingly, the percentage of virus-specific T cells in the lung remained at these high levels long after the acute infection. Pulmonary memory T cells were further studied in a sensitive adoptive transfer system, which allows visualizing polyclonal CD4+ and CD8+ virus-specific memory T cell responses. Fifty days after infection, persisting RSV-specific pulmonary T cells remained CD69hi CD62Llo, but had returned to a resting memory state according to functional criteria. In the absence of neutralizing antibodies reinfection first induced cell division among virus-specific memory T cells 3 days after infection predominantly in the local lymph node. However, divided cells then rapidly accumulated in the lung without significantly increasing in the lymph node. These results suggest rapid export of reactivated cells from the lymph node to the target organ. Thus, although memory T cells can be maintained in the infected organ after a localized virus infection, amplification of a recall response appears to be most effective in organized lymphoid tissue.