Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized blood products: a mechanism for monocyte-mediated suppression of T-cell proliferation.
Previous reports showed that granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMC) are hyporesponsive to alloantigen compared with control PBMC. In the current study, neutralizing antibodies to interleukin-10 (IL-10) increased the proliferative response of G-PBMC to alloantigen by 50. 14% (+/- 12.79%; n = 8), whereas the proliferative response of control PBMC was not affected. The inhibition of OKT3-stimulated CD4 cell proliferation by G-PBMC-derived CD14(+) cells could also be abrogated by the addition of IL-10 neutralizing antibodies. Further, IL-10 levels correlated with the number of CD14 cells in these cultures. Constitutive IL-10 mRNA levels detected by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were 10-fold higher in G-PBMC compared with control PBMC. This translated into significantly higher IL-10 levels after 24-hour lipopolysaccharide (LPS) stimulation of G-PBMC compared with control PBMC (P = .036). IL-10 mRNA levels were also fivefold higher in isolated G-PBMC-derived CD14 cells compared with control CD14 cells. This corresponded to increased constitutive production of IL-10 by isolated G-PBMC-derived CD14 cells compared with control CD14 cells (357.2 +/- 104.5 v 51.7 +/- 30.5, P = .051). In conclusion, these data suggest that monocytes contained within G-PBMC, which, in comparison to marrow, are increased in absolute number and relative proportion to T cells, may suppress T-cell responsiveness by secretion of IL-10.
Mielcarek
M
M
Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Graf
L
L
Johnson
G
G
Torok-Storb
B
B
D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D019138:Antibodies, Blocking; D018950:Lipopolysaccharide Receptors; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor