IL-12 INDIRECTLY ENHANCES PROLIFERATION OF 5-FU-TREATED HUMAN HEMATOPOIETIC PERIPHERAL-BLOOD CD34(+) CELLS

Interleukin-12 (IL-12) or natural killer cell stimulatory factor (NKSF ), has multiple effects on T lymphocytes and natural killer cells, In this study, the effect of IL-12 on human hematopoiesis was studied by analyzing the growth of CD34(+) peripheral blood stem cells (PBSC), in steady state. In the presence of Epo, IL-12 alone or in combination w ith IL-3 or SCF had no effect on the formation of colonies from CD34() cells. In culture with Epo, G-CSF, and IL-3, the effect of Flt3-liga nd (FL) on CD34(+) PBSC was investigated in the presence or absence of IL-12, No additional effect of IL-12 was observed when combined with FL, We evaluated 5-FU-treated human CD34(+) PBSC proliferation in cult ures with Epo, G-CSF, and IL-3, in the presence or absence of IL-12, N o cytokine combination enhanced colony formation from 5-FU-treated CD3 4+ cells, However, in cultures of B-FU-treated human CD34(+) cells, th e most efficient combination was IL-3 + Epo + G-CSF + Accessory cells (CD34(-)). Furthermore, IL-12 enhanced this colony formation significa ntly, To investigate whether immature CD34+ cells were responsible for FL or SCF, 5-FU-treated human CD34(+) cells were cultured with or wit hout IL-12, Whereas no synergistic effect was observed in combination with IL-12, SCF alone significantly enhanced colony formation. However , the colony number was found to be smaller than with the potent combi nation of accessory cells in the presence of IL-12, These results indi cate that accessory cells, lost in CD34(+) cell purification, could be partly responsible for an IL-12 effect on immature human PBSC prolife ration. Am. J, Hematol, 58:183-188, 1998. (C) 1998 Wiley-Liss, Inc.