Origin and fate of lymphocytic choriomeningitis virus-specific CD8+ T cells coexpressing the inhibitory NK cell receptor Ly49G2.
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(high)1B11(high)CD62L(low)) phenotype. By day 8, both subsets synthesized IFN-gamma 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.
Peacock
Craig D
CD
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Welsh
Raymond M
RM
D000375:Aging / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage; D007156:Immunologic Memory; D016130:Immunophenotyping; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000032:analysis*
C452844:Ly49G2 receptor; D011971:Receptors, Immunologic