Bone marrow CD3+ CD56+ regulatory T lymphocytes (TR3 -56 cells) are inversely associated with activation and expansion of bone marrow cytotoxic T cells in IPSS-R very-low/low risk MDS patients.

Abstract

BackgroundEmergence of dysplastic haematopoietic precursor/s, cytopenia and variable leukaemia risk characterise myelodysplastic syndromes (MDS). Impaired immune‐regulation, preferentially affecting cytotoxic T cells (CTL), has been largely observed in MDS. Recently, we described the TR3−56 T cell subset, characterised by the co‐expression of CD3 and CD56, as a novel immune‐regulatory population, able to modulate cytotoxic functions. Here, we address the involvement of TR3−56 cells in MDS pathogenesis/progression.ObjectivesTo analyse the relationship between TR3−56 and CTL activation/expansion in bone marrow (BM) of very‐low/low‐risk MDS subjects.MethodsPeripheral blood and BM specimens, obtained at disease onset in a cohort of 58 subjects, were analysed by immune‐fluorescence and flow cytometry, to preserve the complexity of the biological sample.ResultsWe observed that a trend‐increase of BM TR3−56 in high/very‐high MDS stage, as compared with very‐low/low group, associates with a decreased activation of BM resident CTL; significant correlation of TR3−56 with BM blasts has been also revealed. In addition, in very‐low/low‐risk subjects the TR3−56 amount in BM inversely correlates with the presence of activated BM CTL showing a skewed Vβ T‐cell repertoire.ConclusionsThese data add TR3−56 to the immune‐regulatory network involved in MDS pathogenesis/progression. Better knowledge of the immune‐mediated processes associated with the disease might improve MDS clinical management.