title: Activation of cytotoxic T-cell receptor gammadelta T lymphocytes in response to specific stimulation in myelodysplastic syndromes.
abstract: BACKGROUND
  We previously reported that the function and proliferation of natural killer cells in myelodysplastic syndromes are defective. T-cell receptor gammadelta T cells are other important components of innate immunity that have been recently implicated in the immune response against hematologic malignancies.
  
  
  METHODS
  We evaluated the phenotype, function, and in vitro expansion of myelodysplastic syndrome patient-derived gammadelta T cells in response to interleukin-2 and bromohalohydrin pyrophosphate, a synthetic phosphoantigen with a potent T-cell receptor gammadelta agonist effect that specifically activates and amplifies this T-cell population.
  
  
  RESULTS
  Vgamma9Vdelta2 T cells, the major circulating gammadelta T-cell subset, were reduced in myelodysplastic syndromes, but mainly in myelodysplastic syndromes' patients with associated autoimmune diseases, suggesting that this anomaly was largely due to the autoimmune component. On the other hand, bromohalohydrin pyrophosphate-induced expansion of the Vgamma9Vdelta2 T-cell population in all 15 control samples, but in only 26 of 43 (60%) myelodysplastic syndromes patients. The response to bromohalohydrin pyrophosphate was independent of World Health Organization subtype, cytogenetic findings and International Prognostic Scoring System score. In responding myelodysplastic syndromes patients, expanded Vgamma 9Vdelta2 T cells exhibited normal cytolytic and secretory activity against leukemic and myelodysplastic syndromes cell lines; fluorescence in situ hybridization analysis indicated that these Vgamma 9Vdelta2 T cells were not derived from the myelodysplastic syndromes clone. However, these Vgamma 9Vdelta2 T cells from the MDS patients had limited proliferative capacity in response to interleukin-2 despite having normal expression of interleukin-2 receptor chains (alpha beta gamma ).
  
  
  CONCLUSIONS
  These results, combined with our previous findings concerning natural killer cells, suggest that there are immune surveillance defects in myelodysplastic syndromes, which may contribute to the pathogenesis of these syndromes.
authors.affiliation: INSERM U753, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, 94805, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.forename: Géraldine
authors.initials: G
authors.lastname: Visentin
authors.forename: Emilie
authors.initials: E
authors.lastname: Viey
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
authors.forename: Jerome
authors.initials: J
authors.lastname: Stirnemann
authors.forename: Jean Henri
authors.initials: JH
authors.lastname: Bourhis
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Anne
authors.initials: A
authors.lastname: Caignard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D011756:Diphosphates / Q000494:pharmacology; D005260:Female; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology*; D017404:In Situ Hybridization, Fluorescence; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D011756:Diphosphates; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; C429553:bromohydrin pyrophosphate; D007371:Interferon-gamma