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

Abstract

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.

• Authors: Xiao-su Zhao, Xu-hua Wang, Xiang-yu Zhao, Ying-jun Chang, Lan-ping Xu, Xiao-hui Zhang, Xiao-jun Huang
• Journal: Journal of translational medicine (J Transl Med) Vol. 12 Pg. 187 (Jul 01 2014) ISSN: 1479-5876 [Electronic] England
• PMID: 24984576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• CD4 Antigens
• CD69 antigen
• Cytokines
• Interleukin-2 Receptor alpha Subunit
• Lectins, C-Type

Topics

• Adolescent
• Adult
• Animals
• Antigens, CD (metabolism)
• Antigens, Differentiation, T-Lymphocyte (metabolism)
• Bone Marrow (pathology)
• CD4 Antigens (metabolism)
• Child
• Cytokines (metabolism)
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunomodulation
• Interleukin-2 Receptor alpha Subunit (metabolism)
• Lectins, C-Type (metabolism)
• Leukemia (immunology, pathology)
• Lymphocyte Activation (immunology)
• Lymphocyte Count
• Male
• Mice
• Middle Aged
• Neoplasm Recurrence, Local (immunology)
• Neoplasm, Residual (immunology, pathology)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Transplantation, Homologous