De Alborán I M, Gutierrez J C, Gonzalo J A, Andreu J L, Marcos M A, Kroemer G, Martínez C
Centro de Biología Molecular, CSIC, Universidad Autónoma, Madrid, Spain.
Eur J Immunol. 1992 Apr;22(4):1089-93. doi: 10.1002/eji.1830220432.
MRL/MP-lpr/lpr mice are homozygous for the lpr mutation that results in the accumulation of phenotypically abnormal cells (CD3+CD4+CD8-) in all lymphoid issues. Although no major abnormalities in the T cell receptor repertoire expressed by such lpr cells have been reported, the lpr mutation is a major disease-accelerating factor. Finally, intravenous administration of irradiated lpr cells recovered from the hyperplastic lymph nodes of adult diseased animals to young MRL/Mp-lpr/lpr mice resulted in a highly significant amelioration of disease parameters. This "T cell vaccination" approach resulted in a selective depletion of cells expressing products of the V beta 8.2 subfamily among lymph node T cells, in addition to eliciting a surge in peripheral T cells capable of conferring disease protection in adoptive transfer experiments. Thus, a strategy aimed at specifically reducing the frequency of lpr cells proved successful in mitigating the autoimmune process. These findings add to the involvement of lpr cells in the autoimmune process and constitute the first report that T cell vaccination may be beneficial to a spontaneously occurring autoimmune disease.
MRL/MP-lpr/lpr小鼠为lpr突变的纯合子,该突变导致在所有淋巴组织中出现表型异常细胞(CD3+CD4+CD8-)的积累。尽管尚未有关于此类lpr细胞所表达的T细胞受体库存在重大异常的报道,但lpr突变是一个主要的疾病加速因素。最后,将从成年患病动物增生性淋巴结中回收的经辐照的lpr细胞静脉注射给年轻的MRL/Mp-lpr/lpr小鼠,结果导致疾病参数得到高度显著的改善。这种“T细胞疫苗接种”方法除了引发外周T细胞激增,使其在过继转移实验中能够提供疾病保护外,还导致淋巴结T细胞中表达Vβ8.2亚家族产物的细胞选择性耗竭。因此,一种旨在特异性降低lpr细胞频率的策略被证明在减轻自身免疫过程方面是成功的。这些发现进一步证明了lpr细胞参与自身免疫过程,并且是关于T细胞疫苗接种可能对一种自发发生的自身免疫性疾病有益的首次报道。