Expanded cells in monoclonal TCR-alphabeta+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis recognize hCMV antigens

[EN]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...

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Bibliographic Details
Authors: Rodríguez Caballero, María Arantzazu, García Montero, Andrés Celestino, Bárcena, Paloma, Almeida Parra, Julia María, Ruiz-Cabello, Francisco, Tabernero Redondo, Maria Dolores, Garrido, Pilar, Muñoz Criado, Santiago, Sandberg, Yorick, Langerak, Anton W, González, Marcos, Balanzategui, Ana, Orfao de Matos Correia e Vale, José Alberto
Format: article
Status:Published version
Publication Date:2008
Country:España
Institution:Universidad de Salamanca (USAL)
Repository:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/169292
Online Access:http://hdl.handle.net/10366/169292
Access Level:Open access
Keyword:Immunobiology
Monoclonal CD4+ T-LGL lymphocytosis
Cytomegalovirus
identification and functional characterization of hCMV specific CD4+T cells
Flow cytometry
Genome-wide expression profiling
Antigens
Cluster Analysis
Leukemia
Adult
Humans
Immunity
Lymphocytosis
Oligonucleotide Array Sequence Analysis
Cell Proliferation
Peptide Fragments
Gene Expression Profiling
Antibody Formation
Natural Killer T-Cells
2412 Inmunología
linfocitosis
humanos
leucemia
análisis por grupos
inmunidad
adulto
análisis de secuencias por matrices de oligonucleótidos
perfiles de expresión génica
células T asesinas naturales
proliferación celular
antígenos
fragmentos peptídicos
formación de anticuerpos
citomegalovirus
Description
Summary:[EN]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.

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