Schlaak J F, Löhr H, Gallati H, Meyer zum Büschenfelde K H, Fleischer B
First Department of Medicine, University of Mainz, Germany.
Clin Exp Immunol. 1993 Oct;94(1):168-73. doi: 10.1111/j.1365-2249.1993.tb05996.x.
The pathogenic mechanisms underlying the development of autoimmune hepatitis (AIH) are still unclear. Since AIH is associated with the presence of various autoantibodies and certain HLA subtypes, it is likely that T and B cells play a major role in this disease. In this study we have determined the functional capacities of in vivo preactivated liver-infiltrating T cells (LTC) from patients with AIH. As controls we used LTC from patients with non-autoimmune hepatitis (non-AIH). Our results show that preactivated LTC from patients with AIH predominantly (190/255 clones) reside in the CD4+ population, whereas LTC in non-AIH are dominated by the CD8+ phenotype (148/254 clones). In view of this finding we have investigated the cytokine secretion patterns of 102 randomly chosen CD4+ T cell clones from six patients with AIH. As controls we have used 58 CD4+ LTC from 11 patients with non-AIH. All clones were stimulated by lectin and irradiated accessory cells and subsequent cytokine production was evaluated. LTC from patients with AIH have a lower interferon-gamma (IFN-gamma)/IL-4 ratio compared with LTC from non-AIH. Although clones from some patients with AIH produced very high amounts of IL-4 in vitro, this was not a constant finding. These results show that in vivo preactivated LTC from patients with AIH are mostly CD4+ T cells that produce more IL-4 than IFN-gamma. In contrast, LTC from patients with non-AIH are dominated by CD8+ and CD4+ T cells that produce significantly less IL-4 than IFN-gamma. Thus, liver-infiltrating T cells from patients with AIH and non-AIH belong to different functional T cell subsets. This may have implications for the regulation of humoral and cellular immune responses in inflammatory liver disease.
自身免疫性肝炎（AIH）发病的致病机制仍不清楚。由于AIH与多种自身抗体及某些人类白细胞抗原（HLA）亚型的存在有关，T细胞和B细胞很可能在该病中起主要作用。在本研究中，我们测定了AIH患者体内预先激活的肝浸润性T细胞（LTC）的功能能力。作为对照，我们使用了非自身免疫性肝炎（非AIH）患者的LTC。我们的结果显示，AIH患者预先激活的LTC主要（190/255个克隆）存在于CD4+群体中，而非AIH患者的LTC以CD8+表型为主（148/254个克隆）。鉴于这一发现，我们研究了从6例AIH患者中随机选取的102个CD4+ T细胞克隆的细胞因子分泌模式。作为对照，我们使用了11例非AIH患者的58个CD4+ LTC。所有克隆均用凝集素和经辐照的辅助细胞刺激，随后评估细胞因子的产生情况。与非AIH患者的LTC相比，AIH患者的LTC产生的干扰素-γ（IFN-γ）/白细胞介素-4（IL-4）比值较低。虽然一些AIH患者的克隆在体外产生了非常大量的IL-4，但这并非普遍现象。这些结果表明，AIH患者体内预先激活的LTC大多是产生IL-4多于IFN-γ的CD4+ T细胞。相比之下，非AIH患者的LTC以CD8+和CD4+ T细胞为主，其产生的IL-4明显少于IFN-γ。因此，AIH和非AIH患者的肝浸润性T细胞属于不同的功能性T细胞亚群。这可能对炎症性肝病中体液免疫和细胞免疫反应的调节有影响。
