title: [Differential regulation of CCR5 expression on T lymphocytes in healthy donors after mobilization with rhG-CSF and its correlation with aGVHD].
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.
authors.affiliation: Department of Hematology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Xiang-Juan
authors.initials: XJ
authors.lastname: Ma
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Dong
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Qiu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Mang-Ju
authors.initials: MJ
authors.lastname: Wang
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Sun
authors.forename: Han-Yun
authors.initials: HY
authors.lastname: Ren
mesh_terms: D000293:Adolescent; D000328:Adult; D001782:Blood Donors; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000473:pathology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
chemical_list: C584933:CCR5 protein, human; D019713:Receptors, CCR5; D016179:Granulocyte Colony-Stimulating Factor