Qualitative Differences Between Naive and Memory T Cells Make a Major Contribution to the More Rapid and Efficient Memory CD8+ T Cell Response

Abstract

CD8+ T cells are present at a higher frequency following a primary response, and these memory cells exhibit qualitative differences from naive cells. The importance of these differences vs increased precursor frequency in making a memory response more rapid and efficient has been unclear. Adoptive transfer of 2C TCR transgenic CD8+ T cells into normal recipients, followed by i.p. challenge with allogeneic P815 tumor, results in a long-lived memory population that includes both endogenous host CD8+ T cells and 2C cells. The 2C cells can be identified, using 1B2 mAb specific for the TCR, and thus used as an indicator of the properties of the memory cells. The memory cells have a heterogeneous surface phenotype, and their distribution in lymphoid organs, blood, and peripheral sites is distinct from that of naive cells. Upon rechallenge with Ag, memory cells access the peritoneal cavity much more rapidly than do naive cells (12 h vs 5 days). This appears to result from a requirement for naive cells to interact with Ag before they can efficiently migrate to inflammatory sites, while this is not required for memory cells. In addition, memory cells exhibit some cytolytic activity before rechallenge with Ag, and potent cytolytic activity is present in the peritoneal cavity within 12 h of rechallenge. Comparison of primary and memory responses in mice having similar frequencies of Ag-specific precursors demonstrated that the more rapid migration and the immediate effector function of at least some memory cells contribute very substantially to making a memory response at a peripheral site more rapid and efficient.