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

Abstract

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 (βV) 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-βV 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