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 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. CONCLUSION: 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.
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 MDSpatients, 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 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 MDSpatients. 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 MDSpatients 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.
Authors: Steve Poirier; Samaneh Samami; Maya Mamarbachi; Annie Demers; Ta Yuan Chang; Dennis E Vance; Grant M Hatch; Gaétan Mayer Journal: J Biol Chem Date: 2014-05-22 Impact factor: 5.157
Authors: I Gañán-Gómez; Y Wei; D T Starczynowski; S Colla; H Yang; M Cabrero-Calvo; Z S Bohannan; A Verma; U Steidl; G Garcia-Manero Journal: Leukemia Date: 2015-03-12 Impact factor: 11.528
Authors: Paulo V Campregher; Santosh K Srivastava; H Joachim Deeg; Harlan S Robins; Edus H Warren Journal: Exp Hematol Date: 2009-12-24 Impact factor: 3.084