Effect of recombinant human granulocyte colony-stimulating factor on T-lymphocyte function and the mechanism of this effect.
Whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) affects lymphocyte function directly or indirectly is controversial. In this study, we found that T-cell proliferation was decreased considerably in response to phytohemagglutinin in donors who received rhG-CSF but was partly restored after monocytes were removed. Intracellular cytokine staining revealed that the interferon gamma-interleukin 4 ratio decreased by 5.97-fold in donor CD4+ cells after rhG-CSF treatment. No effect of rhG-CSF on ex vivo T-cell function was observed. rhG-CSF indirectly induced significant quantitative and qualitative changes on lymphocytes, including a decrease in T-cell proliferation and type 2 helper T-cell polarization of the cytokine profile. Although monocytes suppressed T-cell proliferation, the suppressive activity induced by the quantitative change in monocyte numbers cannot completely account for the hyporesponsiveness of T-lymphocytes. We believe that there must be another mediating factor. In addition, the numbers and mean fluorescence intensities of CD14CD86+ cells and CD19+CD80+ cells declined significantly in the peripheral blood after rhG-CSF treatment. Suboptimal amounts of stimulatory signals provided by low expression levels of B7 molecules on antigen-presenting cells (monocytes, B-lymphocytes) may help explain the alteration in T-cell proliferation. In addition, the absolute counts of CD3+CD4-CD8 cells in the peripheral blood were markedly increased and enriched in leukapheresis products following G-CSF treatment. These suppressor cells may contribute to T-cell hyporesponsiveness.
Chen
Song-He
SH
Peking University Institute of Hematology, Peking University People's Hospital, Beijing, People's Republic of China.
Li
Xin
X
Huang
Xiao-Jun
XJ
D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007937:Leukapheresis; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
D018941:Antigens, CD19; D018122:B7-1 Antigen; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D007371:Interferon-gamma