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

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• 作者：Claudio Fozza ; Salvatore Contini ; Antonio Galleu ; Maria Pina Simula ; Patrizia Virdis ; Silvana Bonfigli ; Maurizio Longinotti
• 刊名：Experimental Hematology
• 出版年：2009
• 出版时间：August 2009
• 年：2009
• 卷：37
• 期：8
• 页码：947-955
• 全文大小：623 K

文摘

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.