title: Expanded cells in monoclonal TCR-alphabeta+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis recognize hCMV antigens.
abstract: Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal T-cell receptor (TCR)-alphabeta(+)/CD4(+)/NKa(+)/CD8(-/+dim) T-large granular lymphocyte (LGL) lymphocytosis. Because healthy persons show (oligo)clonal expansions of human cytomegalovirus (hCMV)-specific TCRVbeta(+)/CD4(+)/cytotoxic/memory T cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4(+) T-LGL. Peripheral blood samples from patients with monoclonal TCR-alphabeta(+)/CD4(+) T-LGL lymphocytosis and other T-chronic lymphoproliferative disorders were evaluated for the specific functional response against hCMV and hEBV whole lysates as well as the "MQLIPDDYSNTHSTRYVTVK" hCMV peptide, which is specifically loaded in HLA-DRB1*0701 molecules. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile analysis. Patients with TCR-alphabeta(+)/CD4(+) T-LGL displayed a strong and characteristic hCMV-specific functional response, reproduced by the hCMV peptide in a subset of HLA-DRB1*0701(+) patients bearing TCRVbeta13.1(+) clonal T cells. Gene expression profile showed that the hCMV-induced response affects genes involved in inflammatory and immune responses, cell cycle progression, resistance to apoptosis, and genetic instability. This is the first study providing evidence for the involvement of hCMV in the ontogeny of CD4(+) T-LGL, emerging as a model disorder to determine the potential implications of quite a focused CD4(+)/cytotoxic immune response.
authors.affiliation: Departamento de Medicina, Servicio de Citometría, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Rodríguez-Caballero
authors.forename: Andrés C
authors.initials: AC
authors.lastname: García-Montero
authors.forename: Paloma
authors.initials: P
authors.lastname: Bárcena
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Cabello
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Tabernero
authors.forename: Pilar
authors.initials: P
authors.lastname: Garrido
authors.forename: Santiago
authors.initials: S
authors.lastname: Muñoz-Criado
authors.forename: Yorick
authors.initials: Y
authors.lastname: Sandberg
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Ana
authors.initials: A
authors.lastname: Balanzategui
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao