title: EBV-specific memory CD8+ T cell phenotype and function in stable solid organ transplant patients.
abstract: Immune responses to EBV in immunosuppressed (IS) solid organ transplant (SOTx) recipients have not been well characterized. Here we evaluate the phenotype and function of EBV-specific CD8+ T cells in peripheral blood isolated from "stable" IS SOTx recipients. The EBV-specific CD8+ T cell memory subset distribution in the peripheral blood of patients was examined by flow cytometric analysis using HLA-A2 tetramers incorporating BMLF1 (lytic), and LMP2 and EBNA3A (latent)-derived peptides, in conjunction with mAbs against the CD45RO, CD45RA, and CD62L markers. The ability of CD8+ T cells to produce IFN-gamma in response to the same EBV-derived peptides was measured by ELISPOT assay. Patients and healthy normal donors exhibited similar anti-EBV CD8+ T cell frequencies and specificities against the EBV epitopes evaluated. When compared to healthy normal donors, an overall significant expansion of the CD8+ T cell "effector memory" (CD45RO+/CD62L-) pool, including that of EBV "latent" (LMP2 and EBNA3A)-specific CD8+ T cells was detected in IS SOTx patients. However, the patients' EBV-specific CD8+ T cells showed decreased IFN-gamma production to the EBV-peptide stimulation. These results indicate that the impairment of EBV-specific CD8+ T cell activity is not due to clonal depletion, but is mainly due to impaired functional activation.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Camila
authors.initials: C
authors.lastname: Macedo
authors.forename: Albert
authors.initials: A
authors.lastname: Donnenberg
authors.forename: Iulia
authors.initials: I
authors.lastname: Popescu
authors.forename: Jorge
authors.initials: J
authors.lastname: Reyes
authors.forename: Kareem
authors.initials: K
authors.lastname: Abu-Elmagd
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: John J
authors.initials: JJ
authors.lastname: Fung
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Storkus
authors.forename: Diana
authors.initials: D
authors.lastname: Metes
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019041:L-Selectin / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D019041:L-Selectin; D017493:Leukocyte Common Antigens