Risdon G, Moore T A, Kumar V, Bennett M
Graduate Program in Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235.
Blood. 1991 Nov 1;78(9):2387-91.
Dehydroepiandrosterone (DHEA) is a naturally occurring steroid. We have previously shown that dietary DHEA (0.45% wt/wt) inhibits murine lymphopoiesis but not myelopoiesis. To assess the effect of DHEA on stages of natural killer (NK) cell differentiation, lethally irradiated mice fed DHEA or not were infused with 10(6) or 20 x 10(6) syngeneic bone marrow cells (BMC) as a source of transplantable NK cell progenitors. The differentiation of progenitor cells to lytic NK cells was assessed by the ability to clear radiolabeled YAC-1 tumor cells from the lungs. DHEA-fed recipients of 10(6) or 20 x 10(6) BMC failed to generate NK activity. Because NK progenitor cells are believed to differentiate into interleukin-2 (IL-2)-responsive precursor cells before maturation, BMC from recipient mice were cultured with IL-2 and the generation of NK cells was assessed. DHEA feeding prevented the generation of IL-2-responsive precursor cells in recipients of 10(6) BMC, but this inhibition was overcome in recipients of 20 x 10(6) BMC. To evaluate the capacity of stem cells to generate NK progenitor cells in DHEA-fed mice, the ability of marrow cells from primary recipients to generate NK activity in irradiated secondary recipients was determined. The production of NK progenitors was inhibited 20-fold. Thus, DHEA appears to inhibit the generation of NK progenitors from more primitive stem cells, the differentiation of progenitors into IL-2-responsive precursors cells and the maturation of IL-2-responsive precursor cells into mature NK cells.
脱氢表雄酮（DHEA）是一种天然存在的类固醇。我们之前已经表明，饮食中的DHEA（0.45%重量/重量）会抑制小鼠淋巴细胞生成，但不抑制骨髓生成。为了评估DHEA对自然杀伤（NK）细胞分化阶段的影响，给接受致死性照射且喂食或未喂食DHEA的小鼠输注10⁶或20×10⁶同基因骨髓细胞（BMC），作为可移植NK细胞祖细胞的来源。通过清除肺部放射性标记的YAC - 1肿瘤细胞的能力来评估祖细胞向裂解性NK细胞的分化。接受10⁶或20×10⁶BMC且喂食DHEA的受体未能产生NK活性。由于NK祖细胞被认为在成熟之前会分化为对白介素 - 2（IL - 2）有反应的前体细胞，所以将受体小鼠的BMC与IL - 2一起培养，并评估NK细胞的生成情况。喂食DHEA阻止了接受10⁶BMC的受体中IL - 2反应性前体细胞的生成，但在接受20×10⁶BMC的受体中这种抑制作用被克服。为了评估干细胞在喂食DHEA的小鼠中产生NK祖细胞的能力，确定了初代受体的骨髓细胞在受照射的二代受体中产生NK活性的能力。NK祖细胞的产生被抑制了20倍。因此，DHEA似乎抑制了更原始干细胞产生NK祖细胞、祖细胞分化为IL - 2反应性前体细胞以及IL - 2反应性前体细胞成熟为成熟NK细胞的过程。
