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Activation of cytotoxic T-cell receptor T lymphocytes in response to specific stimulation in myelodysplastic syndromes

¹ INSERM U753, Institut Gustave Roussy, Villejuif
² AP-HP, Hôpital Avicenne, Service d’Hématologie Clinique, Bobigny, and Université Paris 13
³ APHP, Hôpital Saint-Louis, DBIM, Paris
⁴ APHP, Hôpital Avicenne, Laboratoire d’Hématologie, Bobigny
⁵ APHP, Hôpital Jean Verdier, Service de Medecine Interne, Bondy
⁶ Institut Gustave Roussy, Service d’Hématologie, Villejuif, France

Correspondence: Anne Caignard, INSERM U753, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, 94805, France. E-mail: caignard{at}igr.fr

Background: We previously reported that the function and proliferation of natural killer cells in myelodysplastic syndromes are defective. T-cell receptor 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 T cells in response to interleukin-2 and bromohalohydrin pyrophosphate, a synthetic phosphoantigen with a potent T-cell receptor agonist effect that specifically activates and amplifies this T-cell population.

Results: V9V2 T cells, the major circulating 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 V9V2 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 9V2 T cells exhibited normal cytolytic and secretory activity against leukemic and myelodysplastic syndromes cell lines; fluorescence in situ hybridization analysis indicated that these V 9V2 T cells were not derived from the myelodysplastic syndromes clone. However, these V 9V2 T cells from the MDS patients had limited proliferative capacity in response to interleukin-2 despite having normal expression of interleukin-2 receptor chains ( β ).

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.

Key words: innate immunity, myelodysplasia, cellular immunology.