Concurrent naive and memory CD8+ T cell responses to an influenza A virus

Memory Thy-1(+)CD8(+) T cells specific for the influenza A virus nucleoprotein (NP366-374) peptide were sorted after staining with the (DNP366)-N-b tetramer, labeled with CFSE, and transferred into normal Thy-1.2(+) recipients. The donor (DNP366+)-N-b T cells recovered 2 days later from the spleens of the Thy-1.2(+) hosts showed the CD62LwCD44(high)CD69(low) phenotype, characteristic of the population analyzed before transfer, and were present at frequencies equivalent to those detected previously in mice primed once by a single exposure to an influenza A virus. Analysis of CFSE-staining profiles established that resting tetramer(+) T cells divided slowly over the next 30 days, while the numbers in the spleen decreased about 3-fold. Intranasal infection shortly after cell transfer with a noncross-reactive influenza B virus induced some of the donor (DNP366+)-N-b T cells to cycle, but there was no increase in the total number of transferred cells. By contrast, comparable challenge with an influenza A virus caused substantial clonal expansion, and loss of the CFSE label. Unexpectedly, the recruitment of naive Thy-1.2(+)CD8(+)D(b)NP(366)(+) host (DNP366+)-N-b T cells following influenza A challenge was not obviously diminished by the presence of the memory Thy-1.1(+)CD8(+)D(b)NP(366)(+) donor (DNP366+)-N-b set. Furthermore, the splenic response to an epitope (D(b)PA(224)) derived from the influenza acid polymerase (PA(224-233)) was significantly enhanced in the mice given the donor (DNP366+)-N-b memory population. These experiments indicate that an apparent recall response may be comprised of both naive and memory CD8(+) T cells.