Bone marrow CD3 (+) CD56 (+) regulatory T lymphocytes (T(R3) (−56) cells) are inversely associated with activation and expansion of bone marrow cytotoxic T cells in IPSS‐R very‐low/low risk MDS patients

BACKGROUND: Emergence 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 T(R3−56) 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 T(R3−56) cells in MDS pathogenesis/progression. OBJECTIVES: To analyse the relationship between T(R3−56) and CTL activation/expansion in bone marrow (BM) of very‐low/low‐risk MDS subjects. METHODS: Peripheral 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. RESULTS: We observed that a trend‐increase of BM T(R3−56) 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 T(R3−56) with BM blasts has been also revealed. In addition, in very‐low/low‐risk subjects the T(R3−56) amount in BM inversely correlates with the presence of activated BM CTL showing a skewed Vβ T‐cell repertoire. CONCLUSIONS: These data add T(R3−56) 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.