Synergy among erythropoietin, interleukin 3, stem cell factor (c‐kitLigand) and interferon‐gamma on early human hematopoiesis–effect of ifn‐y on early hematopoiesis

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Abstract
The stimulatory effect of interferon‐gamma (IFN‐γ) on human early hematopoiesis was investigated using CD34+ cells that were purified from peripheral blood as a target. In the presence of human interleukin 3 (IL‐3) and stem cell factor (SCF), the growth of colony forming units for granulocyte/macrophage (CFU‐GM) in serum‐free methylcellulose culture was enhanced up to 5.5‐fold over baseline colony formation (n = 10, mean ± SE, 3.18 ± 1.00) by coculture with 2.5 × 103 U/ml IFN‐γ, whereas burst forming units‐erythroid (BFU‐E) growth induced by additional erythropoietin (Epo) was reduced dose‐dependently. Liquid‐suspension culture of the target cells for 24 h with IFN‐γ before secondary plating in serum‐free methylcellulose resulted in a marked increase in the colony numbers; 3.62‐ ± 1.04‐fold for CFU‐GM and 5.72‐ ± 232‐fold for BFU‐E (n = 5). The effect was most striking in the growth of erythroid lineage supported by Epo alone in serum‐free culture. Delayed addition of IFN‐γ between days 4 and 7 of methylcellulose culture suppressed CFU‐GM growth, but not that of BFU‐E. These results suggest that IFN‐γ is an essential cytokine that affects human hematopoiesis and exerts a bimodal effect on stem cell maturation; potentiating or replacing the effect of early‐acting cytokines such as SCF or IL‐3, and suppressing the growth of matured progenitor cells.