Recombinant human granulocyte colony-stimulating factor significantly decreases the expression of CXCR3 and CCR6 on T cells and preferentially induces T helper cells to a T helper 17 phenotype in peripheral blood harvests.
The aim of this study was to investigate the expression of chemokine receptors on T cells and functional changes of T helper (Th) cells in peripheral blood stem cell (PBSC) harvests after treating healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF). Using multiparameter flow cytometry, we analyzed the expression of CXCR3 and CCR6 on T cells and the production of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-17 by CD4(+) Th cells in PBSC grafts of healthy donors after in vivo rhG-CSF application. Alterations in the relative expression levels of T cell receptor beta variable (TCRBV) family members were determined using real-time polymerase chain reaction (PCR). rhG-CSF mobilization significantly decreased the expression of CXCR3 and CCR6 on T cells. Treating donors with rhG-CSF resulted in decreased IFN-gamma production and dramatically increased IL-4 and IL-17 secretion by CD4(+) Th cells, leading to T cell polarization from the Th1 to the Th2 phenotype and a preferential increase in IL-17-producing CD4(+) Th cells. We did not observe any differences in the relative expression levels of TCRBV family members before and after in vivo rhG-CSF application. Our results suggest that the expression of CXCR3 and CCR6 on donor T cells was dramatically downregulated and an IL-17 phenotype of CD4(+) Th cells was preferentially induced in PBSC grafts after treating healthy donors with rhG-CSF. The observed effects of rhG-CSF on T cells may be independent of the relative expression levels of TCRBV family members.
Sun
Li-Xia
LX
Department of Hematology, Peking University First Hospital, Beijing, People's Republic of China.
Ren
Han-Yun
HY
Shi
Yong-Jin
YJ
Wang
Li-Hong
LH
Qiu
Zhi-Xiang
ZX
D000293:Adolescent; D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D054399:Receptors, CCR6 / Q000096:biosynthesis*; D054367:Receptors, CXCR3 / Q000096:biosynthesis*; D011994:Recombinant Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
C106311:CCR6 protein, human; C515187:CXCR3 protein, human; C508598:IL4 protein, human; D020381:Interleukin-17; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4