Löhr H, Treichel U, Poralla T, Manns M, Meyer zum Büschenfelde K H
First Department of Internal Medicine, University of Mainz, Germany.
Clin Exp Immunol. 1992 Apr;88(1):45-9. doi: 10.1111/j.1365-2249.1992.tb03037.x.
Autoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera of patients with autoimmune liver disorders. Liver-infiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with AI-CAH or PBC but not chronic viral hepatitis secreted anti-ASGPR antibodies in vitro. In this study we characterized the influence of liver-infiltrating T cells on the secretion of ASGPR-specific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biopsies of three patients with chronic autoimmune liver disorders (one with AI-CAH, two with PBC) were isolated and investigated for their proliferative response to soluble ASGPR and their helper function provided to autoantibody-secreting B lymphocytes. PBMC from these patients secreted autoantibodies spontaneously in their cell culture supernatants and showed a proliferative response to ASGPR. T cell-depleted PBMC, however, lacked spontaneous antibody secretion. Four CD4+CD8- liver-infiltrating T cell clones showed a proliferative response to ASGPR and also induced spontaneous anti-ASGPR antibody production in cell culture supernatants when added to autologous T cell depleted PBMC. Activated supernatants of these T cell clones failed to induce antibody production. None of seven CD4+CD8- and two CD4-CD8+ T cell clones non-responding to ASGPR provided this help for antibody secretion. Anti-ASGPR secretion in vitro could not be inhibited by the addition of MoAbs raised against monomorphic determinants on HLA class II molecules. The addition of purified ASGPR or polyclonal-activating pokeweed mitogen showed no influence on the production of autoantibodies in these cultures. These data show that B lymphocytes require T cell help for the production of ASGPR-specific antibodies. This help can be provided by ASGPR-responsive T helper cells via cellular interactions.
自身免疫性肝病患者血清中存在抗人去唾液酸糖蛋白受体（ASGPR）的自身抗体。在自身免疫性慢性活动性肝炎（AI-CAH）和原发性胆汁性肝硬化（PBC）患者中，已发现特异性识别ASGPR的肝脏浸润性T细胞克隆。最近，我们发现AI-CAH或PBC患者而非慢性病毒性肝炎患者的外周血单个核细胞（PBMC）在体外可分泌抗ASGPR抗体。在本研究中，我们在细胞培养上清液中，对肝脏浸润性T细胞对自体B细胞分泌ASGPR特异性自身抗体的影响进行了表征。从3例慢性自身免疫性肝病患者（1例AI-CAH，2例PBC）的肝活检组织中分离出T细胞克隆，并研究其对可溶性ASGPR的增殖反应以及为分泌自身抗体的B淋巴细胞提供的辅助功能。这些患者的PBMC在其细胞培养上清液中自发分泌自身抗体，并对ASGPR表现出增殖反应。然而，去除T细胞的PBMC缺乏自发抗体分泌。4个CD4 + CD8 - 肝脏浸润性T细胞克隆对ASGPR表现出增殖反应，当添加到自体去除T细胞的PBMC中时，还可在细胞培养上清液中诱导自发抗ASGPR抗体产生。这些T细胞克隆的活化上清液未能诱导抗体产生。7个对ASGPR无反应的CD4 + CD8 - 和2个CD4 - CD8 + T细胞克隆均未为抗体分泌提供这种帮助。添加针对HLA II类分子单态性决定簇的单克隆抗体不能抑制体外抗ASGPR分泌。添加纯化的ASGPR或多克隆激活剂商陆有丝分裂原对这些培养物中自身抗体的产生没有影响。这些数据表明，B淋巴细胞产生ASGPR特异性抗体需要T细胞的帮助。这种帮助可由对ASGPR有反应的T辅助细胞通过细胞间相互作用提供。
