Non-traditional CD4+CD25−CD69+ regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation

Journal of Translational Medicine

Xiao-jun Huang²  Xiao-hui Zhang¹  Lan-ping Xu¹  Ying-jun Chang¹  Xiang-yu Zhao¹  Xu-hua Wang¹  Xiao-su Zhao¹ 

[1] Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China;Peking-Tsinghua Center for Life Sciences, Beijing 100871, China

关键词: Immunoregulatory;    Leukemia;    Relapse;    Allogeneic Hematopoietic Stem Cell Transplantation;    Regulatory T cells;   

Others  :  1148784
DOI  :  10.1186/1479-5876-12-187

 received in 2014-04-08, accepted in 2014-06-25,  发布年份 2014

【 摘 要 】

Background

Non-traditional CD4+CD25–CD69+ T cells were found to be involved in disease progression in tumor-bearing mouse models and cancer patients recently. We attempted to define whether this subset of T cells were related to leukemia relapse after allogeneic hematopoietic cell transplantation (allo-HSCT).

Methods

The frequency of CD4+CD25–CD69+ T cells among the CD4+ T cell population from the bone marrow of relapsed patients, patients with positive minimal residual disease (MRD+) and healthy donors was examined by flow cytometry. The CD4+CD25-CD69+ T cells were also stained with the intracellular markers to determine the cytokine (TGF-β, IL-2 and IL-10) secretion.

Results

The results showed that the frequency of CD4+CD25–CD69 + T cells was markedly increased in patients in the relapsed group and the MRD + group compared to the healthy donor group. The percentage of this subset of T cells was significantly decreased after effective intervention treatment. We also analyzed the reconstitution of CD4+CD25–CD69+ T cells at various time points after allo-HSCT, and the results showed that this subset of T cells reconstituted rapidly and reached a relatively higher level at +60 d in patients compared to controls. The incidence of either MRD+ or relapse in patients with a high frequency of CD4+CD25-CD69+ T cells (>7%) was significantly higher than that of patients with a low frequency of CD4+CD25-CD69+ T cells at +60 d, +90 d and +270 d after transplant. However, our preliminary data indicated that CD4+CD25-CD69+ T cells may not exert immunoregulatory function via cytokine secretion.

Conclusions

This study provides the first clinical evidence of a correlation between non-traditional CD4+CD25-CD69+ Tregs and leukemia relapse after allo-HSCT and suggests that exploration of new methods of adoptive immunotherapy may be beneficial. Further research related to regulatory mechanism behind this phenomenon would be necessary.

【 授权许可】

   
2014 Zhao et al.; licensee BioMed Central Ltd.

【 图 表 】

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