Phenotypic and functional heterogeneity of EBV epitope-specific CD8+ T cells
Department of Pediatrics; Program in Molecular Medicine
Adolescent; Adult; Antigens, CD45; Antigens, CD80; CD8-Positive T-Lymphocytes; Cell Line, Transformed; Cell Membrane; Epitopes, T-Lymphocyte; Epstein-Barr Virus Nuclear Antigens; HLA-A2 Antigen; Herpesvirus 4, Human; Humans; Immunologic Memory; *Immunophenotyping; Interferon Type II; Isoenzymes; Lymphocyte Activation; Membrane Glycoproteins; Oligopeptides; Perforin; Pore Forming Cytotoxic Proteins; Protein Binding; Receptors, Lymphocyte Homing; T-Lymphocyte Subsets
Life Sciences | Medicine and Health Sciences
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.
J Immunol. 2002 Apr 15;168(8):4184-91.
Journal of immunology (Baltimore, Md. : 1950)
Catalina, Michelle D.; Sullivan, John L.; Brody, Robin M.; and Luzuriaga, Katherine, "Phenotypic and functional heterogeneity of EBV epitope-specific CD8+ T cells" (2002). Open Access Articles. 1121.