|Non-traditional CD4+CD25-CD69+regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation|
|Zhao, Xiao-su1; Wang, Xu-hua1; Zhao, Xiang-yu1; Chang, Ying-jun1; Xu, Lan-ping1; Zhang, Xiao-hui1; Huang, Xiao-jun2|
|关键词||Regulatory t Cells Allogeneic Hematopoietic Stem Cell Transplantation Relapse Leukemia Immunoregulatory|
|刊名||JOURNAL OF TRANSLATIONAL MEDICINE|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, Research & Experimental|
|研究领域[WOS]||Research & Experimental Medicine|
|关键词[WOS]||VERSUS-HOST-DISEASE ; SUPPRESSOR-CELLS ; REGULATORY CELLS ; TOLERANCE ; INFUSION ; MICE ; IMMUNOTHERAPY ; CD4(+)CD25(+) ; INDUCTION ; DEPLETION|
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-beta, 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.
|项目编号||81230013 ; 2011-4022-08 ; Z121107001012085 ; 31200658|
|资助机构||Key Program of National Natural Science Foundation of China ; Scientific Research Foundation for Capital Medicine Development ; Clinical Characteristic Study of Capital Project ; National Natural Science Foundation of China|
|作者单位||1.Peking Univ, Inst Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, Peoples Hosp, Beijing 100044, Peoples R China|
2.Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
|Zhao, Xiao-su,Wang, Xu-hua,Zhao, Xiang-yu,et al. Non-traditional CD4+CD25-CD69+regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2014,12.|
|APA||Zhao, Xiao-su.,Wang, Xu-hua.,Zhao, Xiang-yu.,Chang, Ying-jun.,Xu, Lan-ping.,...&Huang, Xiao-jun.(2014).Non-traditional CD4+CD25-CD69+regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation.JOURNAL OF TRANSLATIONAL MEDICINE,12.|
|MLA||Zhao, Xiao-su,et al."Non-traditional CD4+CD25-CD69+regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation".JOURNAL OF TRANSLATIONAL MEDICINE 12(2014).|