Differential regulation of CCR5 expression on T lymphocytes in healthy donors after mobilization with rhG-CSF and its correlation with aGVHD.
10.7534/j.issn.1009-2137.2013.00.032
- Author:
Meng WANG
1
;
Xiang-Juan MA
;
Yu-Jun DONG
;
Zhi-Xiang QIU
;
Wei LIU
;
Yuan LI
;
Mang-Ju WANG
;
Yu-Hua SUN
;
Han-Yun REN
Author Information
1. Department of Hematology, Peking University First Hospital, Beijing 100034, China.
- Publication Type:Journal Article
- MeSH:
Adolescent;
Adult;
Blood Donors;
Child;
Child, Preschool;
Female;
Gene Expression Regulation;
Graft vs Host Disease;
pathology;
Granulocyte Colony-Stimulating Factor;
pharmacology;
Hematopoietic Stem Cell Mobilization;
Hematopoietic Stem Cell Transplantation;
adverse effects;
Humans;
Male;
Middle Aged;
Receptors, CCR5;
metabolism;
T-Lymphocytes;
drug effects;
metabolism;
Young Adult
- From:
Journal of Experimental Hematology
2013;21(4):979-984
- CountryChina
- Language:Chinese
-
Abstract:
This study was to investigate the differential regulation of CCR5 expression on T cells in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and analyze its correlation with acute graft-versus-host disease (aGVHD) so as to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance. Sixty-eight related healthy donor and their corresponding recipient for allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled in this study. The expression of CCR5 on CD4(+) and CD8(+) T cells in the peripheral blood (PB) before and after mobilization were detected by using flow cytometry (FCM) respectively. According to the changes of CCR5 expression on CD4(+) and CD8(+) T cells, the Sixty-two evaluable donors were divided into the downregulated and unchanged/upregulated (non-downregulated) groups, and the incidence of grades II to IV aGVHD in two groups were compared. The results showed that the mean value of CCR5 expression on CD4(+) and CD8(+) T cells in PB was not different significantly after mobilization (P > 0.05). Apparent inconsistency was showed among different individuals. Thirty-four (50%) donors displayed downregulation of CCR5 expression, while 34 (50%) donors manifested unchanged or upregulated CCR5 expression on CD4(+) T cells. CCR5 expression on CD8(+) T cells was downregulated in 42 (61.8%), unchanged or upregulated in 26 (38.3%) donors. The cumulative incidence of grades II to IV aGVHD in the downregulated and non-downregulated groups for CD4(+) T cells were 16.1% and 41.9% (P = 0.032), and recipients with CCR5 downregulation on CD8(+) T cells showed an increased tendency of developing aGVHD (37.8% vs 16.0%, P = 0.065). In conclusion, rhG-CSF mobilization could lead to differential regulation of CCR5 expression on T cells, which might influence the migration of T cells in vivo, decrease T cell trafficking towards GVHD target organs, and thus reduce the incidence of aGVHD after transplantation.