Concurrent Naive and Memory CD8+ T Cell Responses to an Influenza A Virus

Abstract

Memory Thy-1+CD8+ T cells specific for the influenza A virus nucleoprotein (NP366–374) peptide were sorted after staining with the DbNP366 tetramer, labeled with CFSE, and transferred into normal Thy-1.2+ recipients. The donor DbNP366+ T cells recovered 2 days later from the spleens of the Thy-1.2+ hosts showed the CD62LlowCD44highCD69low 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 DbNP366+ 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+DbNP366+ host DbNP366+ T cells following influenza A challenge was not obviously diminished by the presence of the memory Thy-1.1+CD8+DbNP366+ donor DbNP366+ set. Furthermore, the splenic response to an epitope (DbPA224) derived from the influenza acid polymerase (PA224–233) was significantly enhanced in the mice given the donor DbNP366+ memory population. These experiments indicate that an apparent recall response may be comprised of both naive and memory CD8+ T cells.