Wooley P H, Sud S, Whalen J D, Nasser S
Wayne State University Medical School, Detroit, Michigan, USA.
Arthritis Rheum. 1998 Nov;41(11):2022-31. doi: 10.1002/1529-0131(199811)41:11<2022::AID-ART18>3.0.CO;2-P.
Pristane-induced arthritis (PIA) is an experimental seropositive arthritis that is characterized by serologic and cellular immune abnormalities and is dependent on the presence of a competent CD4+ T cell population. We examined the regulation of PIA by genes of the major histocompatibility complex (MHC) and the Mls-1 loci to determine whether the selection of the T cells that infiltrate arthritic joints is a critical factor in disease susceptibility.
Genetic regulation of PIA was investigated using F1 hybrid and congenic strain analysis to determine the influence of MHC and Mls-1 genes. The T cell receptor Vbeta phenotypes of lymph node cells and T cells infiltrating arthritic joints were examined with 2-color flow cytometry and reverse transcription-polymerase chain reaction techniques.
F1 hybrid offspring from 2 major PIA-susceptible strains (DBA/1 x BALB/c) were resistant to the induction of arthritis because of the interaction between genes of the MHC and the Mls-1 loci, which modified the T cell repertoire. This conclusion was supported by the observed resistance to PIA in BALB/ c-Mls-1a mice, where T cells expressing the Vbeta8.1 and Vbeta6 phenotypes were absent. The receptor phenotype of T cells infiltrating arthritic joints in DBA/1 mice was markedly skewed toward Vbeta8.1 and Vbeta6 compared with the population observed in lymph nodes from either PIA or normal control DBA/1 mice.
The data support the hypothesis that PIA is a T cell-mediated disease. While pristane causes a polyclonal T cell expansion that gives rise to lymphadenopathy, the development of arthritis in susceptible strains of mice occurs due to the preservation of specific T cell subsets with the capacity to infiltrate synovial joints.
pristane诱导的关节炎（PIA）是一种实验性血清阳性关节炎，其特征为血清学和细胞免疫异常，且依赖于有功能的CD4 + T细胞群体的存在。我们研究了主要组织相容性复合体（MHC）基因和Mls-1位点对PIA的调控，以确定浸润关节炎关节的T细胞选择是否是疾病易感性的关键因素。
使用F1杂交和同源近交系分析研究PIA的遗传调控，以确定MHC和Mls-1基因的影响。用双色流式细胞术和逆转录-聚合酶链反应技术检测淋巴结细胞和浸润关节炎关节的T细胞的T细胞受体Vβ表型。
来自2个主要PIA易感品系（DBA/1×BALB/c）的F1杂交后代对关节炎诱导具有抗性，这是由于MHC基因和Mls-1位点之间的相互作用，改变了T细胞库。这一结论得到了BALB/c-Mls-1a小鼠对PIA抗性的支持，该小鼠中不存在表达Vβ8.1和Vβ6表型的T细胞。与PIA或正常对照DBA/1小鼠淋巴结中的细胞群体相比，DBA/1小鼠浸润关节炎关节的T细胞受体表型明显偏向Vβ8.1和Vβ6。
数据支持PIA是一种T细胞介导疾病的假说。虽然pristane导致多克隆T细胞扩增并引起淋巴结病，但易感小鼠品系中关节炎的发生是由于保留了具有浸润滑膜关节能力的特定T细胞亚群。
