Kohler S, Thiel A, Rudwaleit M, Sieper J, Braun J
Campus Benjamin Franklin, Charité Berlin, Germany.
Clin Exp Rheumatol. 2005 Nov-Dec;23(6):840-6.
AS and other spondyloarthritides (SpA) are mostly chronic inflammatory rheumatic diseases characterised by a strong association with HLA B27. Recent data from our group have suggested that AS patients have a diminished secretion capacity of inflammatory cytokines, possibly associated with HLA B27. The aim of this study was to identify CD4+ and CD8+ T cell subsets responsible for the observed lower cytokine secretion capacity in HLA B27-positives.
Highly purified (> 98%) CD4+ and CD8+ T cells of HLA B27-positive AS patients (n = 13), healthy HLA B27-positive (n = 7) and -negative controls (n = 9) were stimulated for 6h with PMA/ Ionomycin and, after fixation, stained for surface markers CD45RA and CD27 and cytokines TNFalpha, IFNgamma, IL-4 and IL-10.
CD27+ CD45RA- memory CD8+ T cells of HLA B27-positive subjects showed a significantly lower percentage of TNFalpha (median 71.4%) and IFNgamma production (median 69.7%) than HLA B27-negative controls (TNFalpha 85.1%; p < or = 0.027; IFNgamma 82.7%, p < or = 0.026). A similar result was also detected in CD27- CD45RA+ effector CD8+ T cells of which 43.2% produced TNFalpha and 66.3% IFNgamma in HLA B27-positive subjects, respectively, compared to 75.6% TNFalpha and 84.4% IFNgamma producing T cells in HLA B27-negatives (p < or = 0.045 and p < or = 0.062, respectively). For all CD4+ T cell subsets no significant differences between HLA B27-positive and HLA B27-negative donors were observed, regarding neither the frequency of IFNgamma, TNFalpha, IL-4 or IL-10 producers nor the coexpression of IFNgamma and IL-4 in memory subsets.
HLA B27-positive subjects are characterized by a low proinflammatory cytokine production in CD8+ effector and memory T cell subsets. This suggests an influence of HLA B27 on cytokine production in antigen-experienced CD8+ T cells.
强直性脊柱炎（AS）及其他脊柱关节炎（SpA）大多为慢性炎症性风湿性疾病，其特点是与HLA - B27密切相关。我们团队的最新数据表明，AS患者炎性细胞因子的分泌能力下降，这可能与HLA - B27有关。本研究的目的是确定导致HLA - B27阳性患者细胞因子分泌能力降低的CD4⁺和CD8⁺T细胞亚群。
用佛波酯（PMA）/离子霉素刺激HLA - B27阳性AS患者（n = 13）、健康HLA - B27阳性者（n = 7）及健康HLA - B27阴性者（n = 9）高度纯化（> 98%）的CD4⁺和CD8⁺T细胞6小时，固定后，对表面标志物CD45RA和CD27以及细胞因子肿瘤坏死因子α（TNFα）、干扰素γ（IFNγ）、白细胞介素 - 4（IL - 4）和白细胞介素 - 10（IL - 10）进行染色。
HLA - B27阳性受试者的CD27⁺CD45RA⁻记忆性CD8⁺T细胞分泌TNFα的百分比（中位数71.4%）和IFNγ的百分比（中位数69.7%）显著低于HLA - B27阴性对照（TNFα为85.1%；p≤0.027；IFNγ为82.7%，p≤0.026）。在CD27⁻CD45RA⁺效应性CD8⁺T细胞中也检测到类似结果，HLA - B27阳性受试者中分别有43.2%的细胞分泌TNFα和66.3%的细胞分泌IFNγ，而HLA - B27阴性者中分泌TNFα的T细胞为75.6%，分泌IFNγ的T细胞为84.4%（p分别≤0.045和p≤0.062）。对于所有CD4⁺T细胞亚群，HLA - B阳性和HLA - B阴性供体之间在IFNγ、TNFα、IL - 4或IL - 10产生细胞的频率以及记忆亚群中IFNγ和IL - 4的共表达方面均未观察到显著差异。
HLA - B27阳性受试者的特征是CD8⁺效应性和记忆性T细胞亚群中促炎细胞因子产生水平较低。这表明HLA - B27对抗原接触过的CD8⁺T细胞中细胞因子产生有影响。
