Patients with myelodysplastic syndromes display several T-cell expansions, which are mostly polyclonal in the CD4+ subset and oligoclonal in the CD8+ subset

Objective Immune dysregulation plays a role in the pathophysiology of myelodysplastic syndromes (MDS), as T-cell clones seem to be involved in the inhibition of hematopoietic precursors. The purpose of this study was to analyze the T-cell receptor (TCR) repertoire of MDS patients, focusing on the third complementarity determining region (CDR3) pattern of their CD4 + and CD8 + lymphocyte expansions. Materials and Methods The study involved 30 patients and 15 age-matched controls. The β -variable ( β V) subfamily flow-cytometry analysis was performed on peripheral CD4 + and CD8 + T-cells. Spectratyping TCR-CDR3 analysis was carried out on isolated helper and cytotoxic T lymphocytes after immunomagnetic separation and reverse-transcriptase polymerase chain reaction. Results We first identified by flow cytometry an increased frequency of expanded βVs in both CD4 + and CD8 + T-cells in MDS patients. We then showed, by spectratyping, that the CDR3 profile was mostly Gaussian in their CD4 + T cells, whereas CD8 + T cells usually showed skewed or oligoclonal CDR3 regions. When we compared spectratyping and flow-cytometry findings in each patient, we showed that most CD4 + lymphocyte expansions detected by flow cytometry had Gaussian CDR3 profiles, whereas most CD8 + expansions were oligoclonal. Conclusion We confirm that in MDS patients the TCR- β V repertoire is overall extremely contracted, especially in cytotoxic T cells. This pattern is mainly determined by selective proliferations of both helper and cytotoxic T cells, which are, however, mostly polyclonal in the former and oligoclonal in the latter. Such a difference, possibly related to the different human leukocyte antigen restriction, could reflect the selective involvement of cytotoxic T cells either in the anti-tumor immune surveillance or in an autoreactive aggression toward hematopoietic precursors.