|
|
Blood, 1 December 2008, Vol. 112, No. 12, pp. 4609-4616.
Prepublished online as a Blood First Edition Paper on September 2, 2008; DOI 10.1182/blood-2008-03-146241.
 Previous Article | Next Article 
Submitted March 24, 2008
Accepted July 25, 2008
Expanded cells in monoclonal TCR  +/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis recognize hCMV antigens
Arancha Rodriguez-Caballero, Andres C Garcia-Montero, Paloma Barcena, Julia Almeida, Francisco Ruiz-Cabello, Maria Dolores Tabernero, Pilar Garrido, Santiago Munoz-Criado, Yorick Sandberg, Anton W Langerak, Marcos Gonzalez, Ana Balanzategui, and Alberto Orfao*
Servicio de Citometria & Departamento de Medicina, Universidad de Salamanca (USAL), Salamanca, Spain
Instituto de Biologia Molecular y Celular del Cancer, Centro de Investigacion del Cancer/IBMCC, (CSIC-USAL), Universidad de Salamanca, Salamanca, Spain
Servicio de Analisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain
Unidad de Investigacion, IECSCYL-Hospital Universitario de Salamanca, Salamanca, Spain
Servicio de Hematologia, Hospital Universitario Virgen de las Nieves, Granada, Spain
Servicio de Microbiologia, Hospital Universitario de Salamanca, Salamanca, Spain
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain
* Corresponding author; email: orfao{at}usal.es.
Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal TCR  +/CD4+/NKa+/CD8-/+dim T-large granular lymphocyte (LGL) lymphocytosis. Since healthy individuals show (oligo)clonal expansions of hCMV- specific TCRV+/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+/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 (GEP) analysis. Patients with TCR+/CD4+ T-LGL displayed a strong and characteristic hCMV-specific functional response, reproduced by the hCMV peptide in a subset of HLA-DRB1*0701+ individuals bearing TCRV13.1+ clonal T-cells. GEP 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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
A "pathogenetic" role for CMV in CD4+ LGL proliferations
- Stephen J. Richards
Blood 2008 112: 4367-4368.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
R. Zambello and G. Semenzato
Large granular lymphocyte disorders: new etiopathogenetic clues as a rationale for innovative therapeutic approaches
Haematologica,
October 1, 2009;
94(10):
1341 - 1345.
[Full Text]
[PDF]
|
|
|
|
|
