title: Classical Hodgkin Lymphoma with Positive Epstein-Barr Virus Status is Associated with More FOXP3 Regulatory T Cells.
abstract: BACKGROUND Classical Hodgkin lymphoma (cHL) is characterized by sparse malignant Hodgkin and Reed-Sternberg cells dispersed in an inflammatory microenvironment. Immune evasion of malignant cells is partially due to the existence of a subpopulation of immunosuppressive regulatory T cells (Treg). The aim of this study was to analyze T cell composition in cHL with special emphasis on Treg in regard to Epstein-Barr virus (EBV) status, subtype, and patient age. MATERIAL AND METHODS The study included 102 patients with cHL diagnosed during a 12-year period. EBV status of cHL was assessed immunohistochemically using antibodies directed to the EBV- encoded LMP1. To define T lymphocyte populations, slides were double-stained with FOXP3 for Treg, and CD4 or CD8 for T cells. In each case the number of single- and/or double-positive cells was counted on an image analyzer in 10 high-power fields. Statistical analysis was performed and differences were considered significant at P<0.05. RESULTS EBV-positive status of cHL was confirmed in 30 (29%) cases, mainly in patients older than 54 years and in mixed cellularity subtype. In EBV-positive cHL, higher numbers of CD8+ cells were found. In cHL with positive EBV status, more FOXP3+ Treg were found, as well as higher numbers of FOXP3+CD4+ Treg compared with EBV-negative cHL. The number of CD4+ cells decreased with age. The frequency of FOXP3+CD8+ Treg was variable, without a statistically significant association with age or EBV status. CONCLUSIONS EBV status has an impact on composition of T cell populations in the cHL microenvironment.
authors.affiliation: Department of Pathology, Forensic Medicine and Cytology, Clinical Hospital Center, Split, Croatia.
authors.forename: Antonia
authors.initials: A
authors.lastname: Pavlovic
authors.affiliation: Department Of Pathology, Forensic medicine and Cytology, Clinical Hospital Center, Split, Croatia.
authors.forename: Merica
authors.initials: M
authors.lastname: Glavina Durdov
authors.affiliation: Department of Nuclear Medicine, Clinical Hospital Center, Split, Croatia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Capkun
authors.affiliation: Department of Hematology, Clinical Hospital, Split, Croatia.
authors.forename: Jasminka
authors.initials: J
authors.lastname: Jakelic Pitesa
authors.affiliation: Department of Oncology, Clinical Hospital, Split, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Bozic Sakic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors