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Department of Microbiology and Immunology, and Emory Vaccine Research Center at Yerkes, Emory University, Atlanta, GA 30329
Memory T cells exhibit a high degree of heterogeneity in terms of their phenotype and functional characteristics. It has been proposed that the CCR7 chemokine receptor divides memory T cell populations into central memory T cells and effector memory T cells with distinct functions in secondary immune responses. We were interested whether this hypothesis holds true in experiments performed on Ag-specific CD8+ T cells. To identify CCR7+ cells, we engineered a fluorescent ligand for CCR7; results with the new CC chemokine ligand 19 chemotetramer were verified by staining with a CCR7 mAb. Staining with the CC chemokine ligand 19 chemotetramer reveals two subsets within CCR7+ cells: a CCR7int population containing memory cells and a CCR7high population containing naive T cells. Phenotypic analysis of MHC class I/peptide tetramer-positive cells revealed that HLA-A2-restricted CMV-specific CD8 T cells exhibit the lowest percentage of CCR7+ cells (0.5–5%), while HLA-A2-restricted flu- and HLA-B8-restricted EBV-specific CD8 T cells showed the highest (45–70%). Intracellular staining of unstimulated cells revealed that both CCR7int- and CCR7--specific CD8 T cells exhibit a detectable level of perforin. Both CCR7int and CCR7- Ag-specific CD8+ T cells produced IFN-
and TNF-
following short-term peptide stimulation. Therefore, our finding that CCR7+CD8+ T cells are able to exert immediate effector functions requires a substantial revision to the central and effector memory hypothesis.
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