期刊
HAEMATOLOGICA
卷 93, 期 3, 页码 381-389出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.11812
关键词
innate immunity; myelodysplasia; cellular immunology
类别
资金
- INSERM
- Fondation de France (Comite Leucemies)
- Association Cent pour Sang la Vie
- AMGEN
Background We previously reported that the function and proliferation of natural killer cells in myelodysplastic syndromes are defective. T-cell receptor gamma delta 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 gamma delta T cells in response to interleukin-2 and bromohalohydrin pyrophosphate, a synthetic phosphoantigen with a potent T-cell receptor gamma delta agonist effect that specifically activates and amplifies this T-cell population. Results V gamma 9V delta 2 T cells, the major circulating gamma delta 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 V gamma 9V delta 2 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 V gamma 9V delta 2 T cells exhibited normal cytolytic and secretory activity against leukemic and myelodysplastic syndromes cell lines; fluorescence in situ hybridization analysis indicated that these V gamma 9V delta 2 T cells were not derived from the myelodysplastic syndromes clone. However, these V gamma 9V delta 2 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 y). 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.
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