Horsfall A C, Mumford P A, Venables P J, Maini R N
Division of Clinical Immunology, Kennedy Institute of Rheumatology, London, UK.
Clin Exp Immunol. 1988 Jan;71(1):62-6.
Peripheral blood mononuclear cells from patients with Sjögren's Syndrome spontaneously secrete autoantibodies to the La antigen when cultured in vitro. This paper reports that specific IgG autoantibody production in vitro is suppressed by pre-treatment of CD8+ enriched T cells with rabbit polyclonal antibodies to idiotypes borne by circulating autologous anti-La antibodies. Treatment of this T cell subpopulation with anti-idiotypes specific for circulating anti-La antibodies from other patients or for anti-DNA antibodies was without effect on anti-La antibody production. Similarly anti-La anti-idiotypes had no effect on the production of autoantibodies to other ribonucleoprotein antigens such as nRNP/Sm. These data show that CD8+ T cells are the main targets for anti-idiotypic control in vitro. We suggest that the relative deficit of these cells, plus a surfeit of CD4+ T cells at the site of the pathological lesion within the salivary gland permits localized production of autoantibodies. Thus, dysregulation of the idiotypic network could contribute to the pathogenesis of Sjögren's Syndrome.
干燥综合征患者的外周血单个核细胞在体外培养时会自发分泌针对La抗原的自身抗体。本文报道,用兔抗循环自身抗La抗体所携带独特型的多克隆抗体预处理富集的CD8⁺T细胞,可抑制体外特异性IgG自身抗体的产生。用针对其他患者循环抗La抗体或抗DNA抗体的独特型抗体处理该T细胞亚群,对抗La抗体的产生没有影响。同样,抗La独特型抗体对针对其他核糖核蛋白抗原(如nRNP/Sm)的自身抗体产生也没有影响。这些数据表明,CD8⁺T细胞是体外抗独特型控制的主要靶点。我们认为,这些细胞的相对缺乏,加上唾液腺病理病变部位CD4⁺T细胞过多,使得自身抗体得以局部产生。因此,独特型网络的失调可能导致干燥综合征的发病机制。