Benfield M R, Vail A, Bucy R P, Weigent D A
Department of Pediatrics, University of Alabama at Birmingham 35233, USA.
Neuroimmunomodulation. 1997 Jan-Feb;4(1):19-27. doi: 10.1159/000097311.
Several reports support the view that growth hormone (GH) promotes proliferation and cytotoxicity by T cells in a mixed leukocyte culture (MLC). The present study was undertaken to begin to determine the mechanism of action of GH on the MLC in vitro. First, we determined that peripheral blood mononuclear cells (PBMC) cultured with mitomycin-treated allogeneic PBMC in an MLC in the presence of exogenously added rhGH develop an augmented proliferative (25-100%) and cytotoxic response (50-600%). We next examined the possibility that GH may promote alloresponses by inducing gamma-interferon (IGN gamma) production. In these experiments, in situ hybridization was used to determine the frequency of cells expressing mRNA for IFN gamma. It was observed that GH increased significantly the frequency of cells expressing mRNA for IFN gamma (100-800%). To determine the site of action of rhGH, we evaluated the response of purified T cells to alloantigens in the presence of rhGH. The addition of rhGH to an MLC had no demonstrable effect when purified T cells were used as the responding population. However, when T cells were reconstituted with autologous mitomycin-treated PBMC and used as the responding population, rhGH augmented proliferation and cytotoxicity. Taken together, these data show that rhGH augments proliferation, cytotoxicity and IFN gamma production during an MLC, and at lease part of the action of rhGH appears to be on the autologous antigen-presenting cell.
几份报告支持这样一种观点,即生长激素(GH)在混合白细胞培养(MLC)中可促进T细胞的增殖和细胞毒性。本研究旨在初步确定GH在体外对MLC的作用机制。首先,我们确定,在外源性添加重组人生长激素(rhGH)的情况下,外周血单个核细胞(PBMC)与经丝裂霉素处理的同种异体PBMC在MLC中培养时,会产生增强的增殖反应(25%-100%)和细胞毒性反应(50%-600%)。接下来,我们研究了GH可能通过诱导γ-干扰素(IFNγ)产生来促进同种异体反应的可能性。在这些实验中,原位杂交用于确定表达IFNγ mRNA的细胞频率。观察到GH显著增加了表达IFNγ mRNA的细胞频率(100%-800%)。为了确定rhGH的作用位点,我们评估了在rhGH存在下纯化T细胞对同种异体抗原的反应。当使用纯化T细胞作为反应群体时,向MLC中添加rhGH没有明显效果。然而,当用自体经丝裂霉素处理的PBMC重建T细胞并将其用作反应群体时,rhGH增强了增殖和细胞毒性。综上所述,这些数据表明rhGH在MLC过程中增强了增殖、细胞毒性和IFNγ的产生,并且rhGH的作用至少部分是针对自体抗原呈递细胞的。