Endogenous naive CD8 T cell precursor frequency and infection type control CD62L gene expression (85.6)

CD62L is essential for homing of lymphocytes to lymph nodes. Moreover, CD62L expression identifies distinct lineages of memory CD8 T cells. However, the factors regulating memory cell lineage differentiation are ill defined. Our data show that CD62L gene regulation is controlled by the input number of transferred antigen-specific CD8 T cells. To enable analysis of endogenous antigen-specific CD8 T cells, we have now utilized a method to enrich naïve antigen-specific CD8 T cells using MHC class I tetramers in conjunction with magnetic bead separation. Of three specificities tested thus far, naïve precursor frequencies ranged from ~100–1000 cells/mouse. Interestingly, following infection with recombinant vesicular stomatitis viruses, the naïve precursor frequency inversely correlated with the time required for the resulting memory population to shift to CD62L+ cells. Remarkably, in the case of ova-specific CD8 T cells, the shift toward CD62L+ ova-specific memory cells occurred substantially faster following infection with Listeria monocytogenes expressing ovalbumin than after VSV-ova infection. This system will allow us to examine parameters of the endogenous CD8 T cell response to infection from initial activation to memory development. This work was supported by NIH grants AI41576 and DK45260 (LL) and a Damon Runyon Foundation fellowship (KMK).