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.