Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic Langerhans cells from cord blood CD34(+) hematopoietic progenitor cells

We have previously shown that tumor necrosis factor (TNF)alpha strongly potentiates the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-3-dependent proliferation of CD34(+) hematopoietic progenitor cells (HPC) through the recruitment of early progenitors with high proliferative potential. Furthermore, the combination of GM-CSF and TNF alpha allows the generation of large numbers of dendritic/Langerhans cells (D-Lc). Herein, we analyzed whether IL-3, when combined to TNF alpha would, as does GM-CSF, allow the generation of CD1a(+) D-Lc. Accordingly, cultures of cord blood CD34(+) HPC with IL-3 + TNF alpha yielded 20% to 60% CD14(+) cells and 11% to 17% CD1a(+) cells, while IL-3 alone did not generate significant numbers of CD1a(+) cells. Although the percentage of CD1a(+) cells detected in IL-3 + TNF alpha was lower than that observed in GM-CSF + TNF alpha (42% to 78%), the strong growth induced by IL-3 + TNF alpha generated as many CD1a(+) cells as did GM-CSF + TNF alpha. The CD14(+) and CD1a(+) cells generated with IL-3 + TNF alpha are similar to CD14(+) and CD1a(+) cells generated in GM-CSF alone and GM-CSF + TNF alpha, respectively. CD1a(+) cells differed from CD14(+) cells by (1) dendritic morphology, (2) higher expression of CD1a, CD1c, CD4, CD40, adhesion molecules (CD11c, CD54, CD58), major histocompatibility complex (MHC) class II molecules and CD28 ligands (CD80 and CD86), (3) lack of Fc receptor Fc gamma RI (CD64) and complement receptor CR1 (CD35) expression, and (4) stronger induction of allogeneic T-cell proliferation. Thus, in combination with TNF alpha, IL-3 is as potent as GM-CSF for the generation of CD1a(+) D-Lc from cord blood CD34(+) HPC. The dendritic cell inducing ability of IL-3 may explain why mice with inactivated GM-CSF gene display dendritic cells. (C) 1996 by The American Society of Hematology.