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...
| Autores: | , , , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2008 |
| País: | España |
| Recursos: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/169292 |
| Acesso em linha: | http://hdl.handle.net/10366/169292 |
| Access Level: | acceso abierto |
| Palavra-chave: | 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 |
| Resumo: | [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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