Albers R, van der Pijl A, Seinen W, Pieters R, Bloksma N
Utrecht University, Research Institute of Toxicology, The Netherlands.
Immunology. 1996 Nov;89(3):468-73. doi: 10.1046/j.1365-2567.1996.d01-755.x.
Bypass of T-cell tolerance via non-cognate graft-versus-host (GVH)-like help from T-helper (Th) cells activated by chemically altered or induced epitopes, has been postulated as a mechanism underlying chemical induction of autoimmunity. To functionally test this hypothesis, we assessed whether the autoimmunogenic chemicals HgCl2 and diphenylhydantoin (DPH), like GVH reactions, stimulate specific immunoglobulin G (IgG) responses to trinitrophenyl (TNP)-Ficoll but not to TNP-ovalbumin. IgG responses were quantified in the popliteal lymph node by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) assays 7 days after s.c. injection of antigens, parental cells, chemicals or combinations thereof into the footpad of semi-allogeneic F1 mice. Antigens, chemicals, or cells alone induced few TNP-specific IgG antibody-forming cell (AFC) compared with untreated mice. Co-injection of parental cells or chemicals with TNP-Ficoll stimulated the TNP-specific response per lymph node approximately 50- and approximately 40-fold, respectively. In contrast, the IgG response to TNP-ovalbumin could not be stimulated by GVH reactions, whereas HgCl2 and DPH dose-dependently increased this response up to approximately 25- and approximately 250-fold, respectively. However, responses to TNP-ovalbumin pre-incubated with HgCl2 or DPH could be stimulated approximately 6-8 fold by GVH reactions. Observed similar adjuvanticity of chemicals and parental cells for TNP-Ficoll support a GVH-like action of autoimmunogenic chemicals. In addition, the chemicals modify TNP-ovalbumin such that B cells recognizing this antigen become susceptible to non-cognate stimulation by GVH reactions.
通过化学改变或诱导的表位激活的辅助性T细胞（Th）提供的非同源移植物抗宿主（GVH）样帮助绕过T细胞耐受性，已被假定为化学诱导自身免疫的潜在机制。为了从功能上验证这一假设，我们评估了自身免疫原性化学物质氯化汞（HgCl2）和苯妥英（DPH）是否像GVH反应一样，刺激针对三硝基苯基（TNP）- 聚蔗糖的特异性免疫球蛋白G（IgG）反应，而不刺激针对TNP - 卵清蛋白的反应。在将抗原、亲代细胞、化学物质或其组合皮下注射到半同种异体F1小鼠足垫7天后，通过酶联免疫吸附斑点形成细胞测定（ELISPOT）在腘窝淋巴结中对IgG反应进行定量。与未处理的小鼠相比，单独的抗原、化学物质或细胞诱导的TNP特异性IgG抗体形成细胞（AFC）很少。将亲代细胞或化学物质与TNP - 聚蔗糖共同注射分别刺激每个淋巴结的TNP特异性反应约50倍和约40倍。相反，GVH反应不能刺激对TNP - 卵清蛋白的IgG反应，而HgCl2和DPH分别以剂量依赖性方式将该反应增加至约25倍和约250倍。然而，对与HgCl2或DPH预孵育的TNP - 卵清蛋白的反应可被GVH反应刺激约6 - 8倍。观察到化学物质和亲代细胞对TNP - 聚蔗糖具有相似的佐剂活性，支持自身免疫原性化学物质的GVH样作用。此外，化学物质修饰TNP - 卵清蛋白，使得识别该抗原的B细胞变得易受GVH反应的非同源刺激。
