Immediate early effector functions of virus-specific CD8+CCR7+ memory cells in humans defined by HLA and CC chemokine ligand 19 tetramers.
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 CCR7(int) population containing memory cells and a CCR7(high) 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 CCR7(int)- and CCR7(-)-specific CD8 T cells exhibit a detectable level of perforin. Both CCR7(int) and CCR7(-) Ag-specific CD8(+) T cells produced IFN-gamma and TNF-alpha 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.
Ravkov
Eugene V
EV
Department of Microbiology and Immunology, and Emory Vaccine Research Center at Yerkes, Emory University, Atlanta, GA 30329, USA.
Myrick
Christy M
CM
Altman
John D
JD
D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000138:chemical synthesis / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D006680:HLA Antigens / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D007156:Immunologic Memory; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D010957:Plasmids; D052899:Pore Forming Cytotoxic Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology
C515460:CCL19 protein, human; C515370:CCR7 protein, human; D016827:CD8 Antigens; D054415:Chemokine CCL19; D019742:Chemokines, CC; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D054353:Perforin