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Concurrent Naive and Memory CD8⁺ T Cell Responses to an Influenza A Virus¹

Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105

Memory Thy-1⁺CD8⁺ T cells specific for the influenza A virus nucleoprotein (NP_366–374) peptide were sorted after staining with the D^bNP₃₆₆ tetramer, labeled with CFSE, and transferred into normal Thy-1.2⁺ recipients. The donor D^bNP₃₆₆⁺ T cells recovered 2 days later from the spleens of the Thy-1.2⁺ hosts showed the CD62L^lowCD44^highCD69^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 D^bNP₃₆₆⁺ 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^bNP₃₆₆⁺ host D^bNP₃₆₆⁺ T cells following influenza A challenge was not obviously diminished by the presence of the memory Thy-1.1⁺CD8⁺D^bNP₃₆₆⁺ donor D^bNP₃₆₆⁺ set. Furthermore, the splenic response to an epitope (D^bPA₂₂₄) derived from the influenza acid polymerase (PA_224–233) was significantly enhanced in the mice given the donor D^bNP₃₆₆⁺ memory population. These experiments indicate that an apparent recall response may be comprised of both naive and memory CD8⁺ T cells.

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