Duchmann R, Lambert C, May E, Höhler T, Märker-Hermann E
Internal Medicine II, University of the Saarland, Hamberg. inrduc2med-rz.uni-sb.de
Clin Exp Immunol. 2001 Feb;123(2):315-22. doi: 10.1046/j.1365-2249.2001.01440.x.
Ankylosing spondylitis (AS) is a complex genetic disease in which both MHC and non-MHC genes determine disease susceptibility. To determine whether the T cell repertoires of individuals with AS show signs of increased stimulation by exogenous antigens, CD4+ and CD8+ T cell subsets of five monozygotic HLA-B27+ twins (two concordant and three discordant for AS) and CD8+ T cell repertoires of three healthy HLA-B27+ individuals were characterized by TCR beta-chain (TCRB) CDR3 size spectratyping. Selected TCRB-CDR3 spectra were further analysed by BJ-segment analysis and TCRB-CDR3 from expanded T cell clones were sequenced. In an analysis of all data (519/598 possible TCRB-CDR3 spectra), AS was associated with increased T cell oligoclonality in both CD8+ (P = 0.0001) and CD4+ (P = 0.033) T cell subsets. This was also evident when data were compared between individual twins. Nucleotide sequence analysis of expanded CD8+ or CD4+ T cell clones did not show selection for particular TCRB-CDR3 amino acid sequence motifs but displayed sequence homologies with published sequences from intra-epithelial lymphocytes or synovial T cells from rheumatoid arthritis patients. Together, these results provide support for the hypothesis that responses to T cell-stimulating exogenous or endogenous antigens are involved in the induction and/or maintenance of AS.
强直性脊柱炎（AS）是一种复杂的遗传性疾病，其中MHC和非MHC基因都决定疾病易感性。为了确定AS患者的T细胞库是否显示出受外源性抗原刺激增加的迹象，通过TCRβ链（TCRB）CDR3大小谱型分析对5对单卵HLA - B27 +双胞胎（2对AS一致，3对AS不一致）的CD4 +和CD8 + T细胞亚群以及3名健康HLA - B27 +个体的CD8 + T细胞库进行了表征。通过BJ片段分析进一步分析选定的TCRB - CDR3谱，并对扩增的T细胞克隆的TCRB - CDR3进行测序。在对所有数据（519/598个可能的TCRB - CDR3谱）的分析中，AS与CD8 +（P = 0.0001）和CD4 +（P = 0.033）T细胞亚群中T细胞寡克隆性增加相关。当在个体双胞胎之间比较数据时，这一点也很明显。扩增的CD8 +或CD4 + T细胞克隆的核苷酸序列分析未显示对特定TCRB - CDR3氨基酸序列基序的选择，但显示出与类风湿性关节炎患者上皮内淋巴细胞或滑膜T细胞的已发表序列具有序列同源性。总之，这些结果为以下假设提供了支持，即对T细胞刺激的外源性或内源性抗原的反应参与了AS的诱导和/或维持。
