van den Bosch G, Preijers F, Vreugdenhil A, Hendriks J, Maas F, De Witte T
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Clin Exp Immunol. 1995 Sep;101(3):515-20. doi: 10.1111/j.1365-2249.1995.tb03143.x.
GM-CSF is known to accelerate haematopoietic recovery following allogeneic bone marrow transplantation (BMT). In addition, it may restore and enhance both granulocyte and monocyte functions. Stimulation of monocyte functions may induce a direct or an indirect anti-leukaemic activity due to an increase of cellular cytotoxicity and production of cytokines which may result in a reduction of the relapse rate after BMT. NK cells may play a crucial role in this activity. Therefore we studied the influence of monocytes on NK activity in combination with GM-CSF. Lymphocytes and monocytes were isolated from buffy coats of healthy individuals by counterflow centrifugation elutriation (CCE). NK activity was exerted by CD3-CD56+ cell populations and could be enhanced by IL-2 incubation overnight. Incubation of CD3-CD56+ cells with GM-CSF in the presence or absence of IL-2 hardly influenced NK activity of the lymphocyte population. Low amounts of monocytes enhanced NK activity. NK activity in lymphocyte population in the presence of equivalent numbers of monocytes with or without IL-2 was strongly decreased irrespective of the effector:target ratio (ETR). This appeared not to result from sterical hindrance effects of the present number of cells. However, addition of GM-CSF abrogated the inhibition of NK activity by monocytes in the presence of IL-2. In monocyte fractions neither IL-2 nor GM-CSF yielded NK activity. Our findings indicate that GM-CSF can affect NK activity by counteracting the suppressing effects of monocytes, and hence may improve the outcome after BMT.
已知粒细胞-巨噬细胞集落刺激因子(GM-CSF)可加速异基因骨髓移植(BMT)后的造血恢复。此外,它还可能恢复并增强粒细胞和单核细胞的功能。刺激单核细胞功能可能会由于细胞毒性增加和细胞因子产生而诱导直接或间接的抗白血病活性,这可能导致BMT后复发率降低。自然杀伤细胞(NK细胞)可能在这一活性中起关键作用。因此,我们研究了单核细胞与GM-CSF联合对NK活性的影响。通过逆流离心淘析法(CCE)从健康个体的血沉棕黄层中分离淋巴细胞和单核细胞。NK活性由CD3-CD56+细胞群体发挥,并且通过过夜孵育白细胞介素-2(IL-2)可增强。在有或无IL-2的情况下,用GM-CSF孵育CD3-CD56+细胞几乎不影响淋巴细胞群体的NK活性。少量单核细胞可增强NK活性。无论效应细胞与靶细胞比例(ETR)如何,在有或无IL-2的情况下,存在等量单核细胞时淋巴细胞群体中的NK活性均显著降低。这似乎不是由于当前细胞数量的空间位阻效应导致的。然而,添加GM-CSF可消除IL-2存在时单核细胞对NK活性的抑制作用。在单核细胞组分中,IL-2和GM-CSF均未产生NK活性。我们的研究结果表明,GM-CSF可通过抵消单核细胞的抑制作用来影响NK活性,因此可能改善BMT后的结果。