CD8 ⁺ T cells responding to influenza infection reach and persist at higher numbers than CD4 ⁺ T cells independently of precursor frequency

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 antigen-specific CD4 ⁺ and CD8 ⁺ T cells.