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Monocyte differentiation and accessory function: different effects on the proliferative responses of an autoreactive T cell clone as compared to alloreactive or antigen-specific T cell lines and primary mixed lymphocyte cultures

机译:单核细胞分化和辅助功能:与同种反应性或抗原特异性T细胞系和原代混合淋巴细胞培养物相比,对自身反应性T细胞克隆的增殖反应的影响不同

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摘要

An autoreactive T cell clone derived from a patient with reactive arthritis, two alloreactive T cell lines, two antigen-specific T cell lines and allogeneic resting T cells were analyzed for their responses to monocytes and macrophages derived from monocytes by in vitro differentiation. The autoreactive T cell clone strongly proliferated in response to fresh monocytes and to macrophages derived from a 7 day culture, but only poorly to monocytes cultured for 2 days. In contrast, alloreactive and antigen-specific T cell lines proliferated to all stimulatory cells equally well. Finally, primary mixed lymphocyte reactions could be stimulated by both fresh and 2-day cultured monocytes, but not by in vitro derived macrophages. The impaired response of the autoreactive T cell clone to 2-day cultured monocytes could not be attributed to reduced expression of several well-defined surface molecules nor to induction of nonresponsiveness. Neither allogeneic monocytes nor cytokines (IL-1, IL-2, IL-4, IL-6) could correct the defective response of the autoreactive T cell clone. However, preculture of monocytes in the presence of interferon-gamma, IL-1, IL-4 or IL-6 retained their stimulatory capacity. Our interpretation of the selectively impaired response of the autoreactive T cell clone is that it most likely recognizes a differentiation-dependent monocyte/macrophage-specific peptide.
机译:通过体外分化,分析了来自患有反应性关节炎的患者,两种同种异体反应性T细胞系,两种抗原特异性T细胞系和同种异体静息T细胞的自身反应性T细胞克隆对单核细胞和源自单核细胞的巨噬细胞的反应。自身反应性T细胞克隆在响应新鲜单核细胞和源自7天培养的巨噬细胞时会强烈增殖,但对培养2天的单核细胞则反应较弱。相反,同种反应性和抗原特异性T细胞系同样良好地增殖到所有刺激细胞。最后,新鲜和2天培养的单核细胞均可刺激原发性混合淋巴细胞反应,而体外衍生的巨噬细胞则不能。自身反应性T细胞克隆对培养2天的单核细胞的应答受损,既不能归因于几种明确定义的表面分子表达的降低,也不能归因于无应答的诱导。同种异体单核细胞和细胞因子(IL-1,IL-2,IL-4,IL-6)都不能纠正自身反应性T细胞克隆的缺陷反应。但是,在存在干扰素-γ,IL-1,IL-4或IL-6的情况下,单核细胞的预培养保留了其刺激能力。我们对自身反应性T细胞克隆选择性受损反应的解释是,它最有可能识别分化依赖性单核细胞/巨噬细胞特异性肽。

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