IL-2 production by virus- and tumor-specific human CD8 T cells is determined by their fine specificity.
Memory CD8 T cells mediate rapid and effective immune responses against previously encountered Ags. However, these cells display considerable phenotypic and functional heterogeneity. In an effort to identify parameters that correlate with immune protection, we compared cell surface markers, proliferation, and cytokine production of distinct virus- and tumor-specific human CD8 populations. Phenotypic analysis of epitope-specific CD8 T cells showed that Ag specificity is associated with distinct CCR7/CD45RA expression profiles, suggesting that Ag recognition drives the expression of these molecules on effector/memory T cells. Moreover, the majority of central memory T cells (CD45RAlowCCR7dull) secreting cytokines in response to an EBV epitope produces both IL-2 and IFN-gamma, whereas effector memory CD8 cells (CD45RAdullCCR7-) found in EBV, CMV, or Melan-A memory pools are mostly composed of cells secreting exclusively IFN-gamma. However, these various subsets, including Melan-A-specific effector memory cells differentiated in cancer patients, display similar Ag-driven proliferation in vitro. Our findings show for the first time that human epitope-specific CD8 memory pools differ in IL-2 production after antigenic stimulation, although they display similar intrinsic proliferation capacity. These results provide new insights in the characterization of human virus- and tumor-specific CD8 lymphocytes.
IDM (Immuno-Designed Molecules) Research Laboratory, University of Pierre et Marie Curie, Paris, France.
Eric
E
Mallard
Frédérique
F
Vernel-Pauillac
Thierry
T
Velu
Frédéric
F
Lehmann
Jean-Pierre
JP
Abastado
Margarita
M
Salcedo
Nadège
N
Bercovici
D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis
D000951:Antigens, Neoplasm; C515370:CCR7 protein, human; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; C072011:MAGEA1 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens