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.


METHODS
The study involved 30 patients and 15 age-matched controls. The beta-variable (betaV) 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 betaVs 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.


CONCLUSIONS
We confirm that in MDS patients the TCR-betaV 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.
Fozza
Claudio
C
Institute of Hematology, University of Sassari, Sassari, Italy. cfozza@uniss.it
Contini
Salvatore
S
Galleu
Antonio
A
Simula
Maria Pina
MP
Virdis
Patrizia
P
Bonfigli
Silvana
S
Longinotti
Maurizio
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D022801:Complementarity Determining Regions / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic
D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta