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The activation, localization, phenotypic changes, and function of CFSE-labeled naive influenza-specific CD8+ and CD4+ T cells following influenza infection were examined. Response of adoptively transferred CD8+ T cells was seen earliest in draining lymph node. Highly activated cells were found later in the lung, airways, and spleen, were cytolytic, and expressed IFN-γ upon restimulation. Similar amounts of division at early time points, but higher numbers of CD8+ T cells, were detected at 9 and 30 days postinfection after cotransfer of CD4+ and CD8+ T cells followed by infection. Transfer of much smaller numbers of CD4+ and CD8+ T cells led to more extensive expansion but the same difference in final number between the two cell types. These studies demonstrate how CD8+ and CD4+ T cells respond to influenza at early time points postinfection and the differential kinetics of antigenspecific CD4+ and CD8+ T cells.