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Origin and Fate of Lymphocytic Choriomeningitis Virus-Specific CD8⁺ T Cells Coexpressing the Inhibitory NK Cell Receptor Ly49G2 ¹

Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655

CD8⁺ T cells that coexpress the inhibitory NK cell receptor, Ly49G2 (G2), are present in immunologically naive C57BL/6 mice but display Ags found on memory T cells. To assess how G2⁺CD8⁺ cells relate to bona fide memory cells, we examined the origin and fate of lymphocytic choriomeningitis virus (LCMV)-induced G2⁺CD8⁺ cells. During early (day 4) acute LCMV infection, both G2⁺ and G2^–CD8⁺ T cell subsets underwent an attrition in number and displayed an activation (CD69^high1B11^highCD62L^low) phenotype. By day 8, both subsets synthesized IFN- in response to immunodominant LCMV peptides, though the expansion of G2⁺ cells was less than that of G2^– cells. Adoptive transfer experiments with purified G2^– or G2⁺CD8⁺ cells from naive mice indicated that the LCMV-specific G2⁺ subset was derived from a pre-existing G2⁺ population and not generated from G2^– cells responding to LCMV infection. Their participation in the LCMV-specific T cell response increased with age, reflecting an increase in the size of the pre-existing G2⁺ pool. Following establishment of stable LCMV memory, the proportion of CD8⁺ cells coexpressing G2 was reduced in comparison to naive controls, presumably due to displacement by G2^– LCMV-specific memory cells. LCMV-specific G2⁺ cells were present in the memory pool, but at low frequencies, and they did not exhibit the typical phenotypic changes of reactivation during secondary challenge. We suggest that G2⁺CD8⁺ cells represent a cell lineage distinct from bona fide memory T cells, but that they can participate in an acute virus-specific T cell response.

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