Phenotypic and functional heterogeneity of EBV epitope-specific CD8+ T cells.
High frequencies of EBV-specific CD8(+) T cells have been detected during acute EBV infection, yet persistent infection inevitably results. To address this issue, we characterized the phenotype and function of epitope-specific CD8(+) T cell populations from presentation with acute through latent infection. Considerable phenotypic and functional heterogeneity within, as well as between, two different epitope-specific populations was observed over time following acute infection. B7 EBV-encoded nuclear Ag (EBNA)-3A-specific CD8(+) T cells expressed only CD45RO from acute through latent EBV infection. A2 BMLF-1-specific CD8(+) T cells expressed CD45RO during acute infection and either CD45RA or CD45RO during latent EBV infection. This difference in CD45 isoform expression between the two epitope-specific populations did not translate into differences in perforin content, the ability to produce IFN-gamma, or the ability to proliferate in response to Ag in vitro. In individuals with latent EBV infection, the frequencies of A2 BMLF-1- or B7 EBNA-3A-specific CD8(+) T cells that expressed CD45RA, CD45RO, CD62 ligand, CCR7, and perforin were stable over time. However, the expression of CD62 ligand and CCR7 was significantly higher among EBNA-3A-specific CD8(+) T cells than among BMLF-1-specific CD8(+) T cells. Further work is necessary to understand how phenotypic and functional differences between EBV epitope-specific CD8(+) T cells are related to the biology of the virus and to the equilibrium between the virus and the host during persistent infection.
Catalina
Michelle D
MD
Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Sullivan
John L
JL
Brody
Robin M
RM
Luzuriaga
Katherine
K
D000293:Adolescent; D000328:Adult; D018122:B7-1 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis* / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011485:Protein Binding / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D018122:B7-1 Antigen; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D015789:HLA-A2 Antigen; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D052899:Pore Forming Cytotoxic Proteins; D016201:Receptors, Lymphocyte Homing; C403195:glycyl-leucyl-cysteinyl-threonyl-leucyl-valyl-alanyl-methionyl-leucine; D054353:Perforin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens