Activation of cytotoxic T-cell receptor γδ T lymphocytes in response to specific stimulation in myelodysplastic syndromes
| Autor: | Jean-Jacques Kiladjian, Géraldine Visentin, Emilie Viey, Sylvie Chevret, Virginie Eclache, Jerome Stirnemann, Jean Henri Bourhis, Salem Chouaib, Pierre Fenaux, Anne Caignard |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Haematologica, Vol 93, Iss 3 (2008) |
| Druh dokumentu: | article |
| ISSN: | 0390-6078 1592-8721 |
| DOI: | 10.3324/haematol.11812 |
| Popis: | Background We previously reported that the function and proliferation of natural killer cells in myelodysplastic syndromes are defective. T-cell receptor γδ T cells are other important components of innate immunity that have been recently implicated in the immune response against hematologic malignancies.Design and Methods We evaluated the phenotype, function, and in vitro expansion of myelodysplastic syndrome patient-derived γδ T cells in response to interleukin-2 and bromohalohydrin pyrophosphate, a synthetic phosphoantigen with a potent T-cell receptor γδ agonist effect that specifically activates and amplifies this T-cell population.Results Vγ9Vδ2 T cells, the major circulating γδ 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 Vγ9Vδ2 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 Vγ 9Vδ2 T cells exhibited normal cytolytic and secretory activity against leukemic and myelodysplastic syndromes cell lines; fluorescence in situ hybridization analysis indicated that these Vγ 9Vδ2 T cells were not derived from the myelodysplastic syndromes clone. However, these Vγ 9Vδ2 T cells from the MDS patients had limited proliferative capacity in response to interleukin-2 despite having normal expression of interleukin-2 receptor chains (α β γ ).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. |
| Databáze: | Directory of Open Access Journals |
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