Bagby G C, Rigas V D, Bennett R M, Vandenbark A A, Garewal H S
J Clin Invest. 1981 Jul;68(1):56-63. doi: 10.1172/jci110254.
Colony-stimulating activities (CSA) are potent granulopoietic stimulators in vitro. Using clonogenic assay techniques, we analyzed the degree to which mononuclear phagocytes and T lymphocytes cooperate in the positive (production/release of CSA) and feedback (inhibition of CSA production/release) regulation of granulopoiesis. We measured the effect of lactoferrin (a putative feedback regulator of CSA production) on CSA provision in three separate assay systems wherein granulocyte colony growth of marrow cells from 22 normal volunteers was stimulated by (a) endogenous CSA-producing cells in the marrow cells suspension, (b) autologous peripheral blood leukocytes in feeder layers, and (c) medium conditioned by peripheral blood leukocytes. The CSA-producing cell populations in each assay were varied by using cell separation techniques and exposure of isolated T lymphocytes to methylprednisolone or to monoclonal antibodies to surface antigens and complement. We noted that net CSA production increased more than twofold when a small number of unstimulated T lymphocytes were added to monocyte cultures. Lactoferrin's inhibitory effect was also T lymphocyte dependent. The T lymphocytes that interact with monocytes and lactoferrin to inhibit CSA production are similar to those that augment CSA production because their activities are neither genetically restricted not glucocorticoid sensitive, and both populations express HLA-DR (Ia-like) and T3 antigens but not T4 or T8 antigens. These findings are consistent with results of our studies on the mechanism of lactoferrin's inhibitory effect with indicate that mononuclear phagocytes produce both CSA and soluble factors that stimulate T lymphocytes to produce CSA, and that lactoferrin does not suppress monocyte CSA production, but does completely suppress production or release by monocytes of those factors that stimulate T lymphocytes to produce CSA. We conclude that mononuclear phagocytes and a subset of T lymphocytes exhibit important complex interactions in the regulation of granulopoiesis.
集落刺激活性（CSA）在体外是强大的粒细胞生成刺激剂。我们运用克隆形成测定技术，分析了单核吞噬细胞和T淋巴细胞在粒细胞生成的正向调节（CSA的产生/释放）和反馈调节（CSA产生/释放的抑制）中协同作用的程度。我们在三个不同的测定系统中测量了乳铁蛋白（一种假定的CSA产生反馈调节因子）对CSA供应的影响，在这些系统中，来自22名正常志愿者的骨髓细胞的粒细胞集落生长受到以下因素刺激：（a）骨髓细胞悬液中内源性产生CSA的细胞，（b）饲养层中的自体外周血白细胞，以及（c）外周血白细胞条件培养基。通过使用细胞分离技术以及将分离的T淋巴细胞暴露于甲基强的松龙或表面抗原和补体的单克隆抗体，改变每个测定中产生CSA的细胞群体。我们注意到，当向单核细胞培养物中添加少量未刺激的T淋巴细胞时，净CSA产生增加了两倍多。乳铁蛋白的抑制作用也依赖于T淋巴细胞。与单核细胞和乳铁蛋白相互作用以抑制CSA产生的T淋巴细胞与增强CSA产生的T淋巴细胞相似，因为它们的活性既不受遗传限制也对糖皮质激素不敏感，并且这两种细胞群体均表达HLA - DR（Ia样）和T3抗原，但不表达T4或T8抗原。这些发现与我们关于乳铁蛋白抑制作用机制的研究结果一致，表明单核吞噬细胞既产生CSA又产生刺激T淋巴细胞产生CSA的可溶性因子，并且乳铁蛋白不抑制单核细胞CSA的产生，但确实完全抑制单核细胞产生或释放那些刺激T淋巴细胞产生CSA的因子。我们得出结论，单核吞噬细胞和一部分T淋巴细胞在粒细胞生成的调节中表现出重要的复杂相互作用。
