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 hypores ponsive to alloantigen compared with control PBMC. In the current stud y, neutralizing antibodies to interleukin-10 (IL-10) increased the pro liferative response of G-PBMC to alloantigen by 50.14% (+/- 12.79%; n = 8), whereas the proliferative response of control PBMC was not affec ted. The inhibition of OKT3-stimulated CD4 cell proliferation by G-PBM C-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 react ion (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 P BMC (P = .036), IL-10 mRNA levels were also fivefold higher in isolate d G-PBMC-derived CD14 cells compared with control CD14 cells. This cor responded to increased constitutive production of IL-10 by isolated G- PBMC-derived CD14 cells compared with control CD14 cells (357.2 +/- 10 4.5 v 51.7 +/- 30.5, P = .051). In conclusion, these data suggest that monocytes contained within G-PBMC, which, in comparison to marrow, ar e increased in absolute number and relative proportion to T cells, may suppress T-cell responsiveness by secretion of IL-10. (C) 1998 by The American Society of Hematology.