Jacobs M J, van den Hoek A E, van de Putte L B, van den Berg W B
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Immunology. 1994 Jun;82(2):294-300.
Intravenous (i.v.) injection of an antigen before immunization has been shown to be a potent way to induce suppression at the T-cell level. In this study we demonstrate an almost complete suppression of arthritis (using antigen-induced arthritis as a model) by i.v. injection of 100 micrograms hen egg lysozyme (HEL) 7 days before immunization. Underlying mechanisms, including suppression by CD8+ T lymphocytes, suppression by T-helper 2 (Th2) or anergy of antigen-specific T lymphocytes, were studied. In vivo treatment with either anti-CD8 or anti-interleukin-4 (IL-4) could not abrogate i.v.-induced tolerance. Lymphocyte stimulation assays showed reduced antigen-specific proliferative responses and IL-2 production in tolerized mice. The possible role of soluble suppressive cytokines was examined in vitro by adding anti-IL-4, anti-IL-10 or anti-transforming growth factor-beta (TGF-beta). Neutralization of these factors could not diminish suppression. Finally, anergy of antigen-specific T lymphocytes was tested as a possible mechanism for i.v.-induced tolerance. Results demonstrated that reduced proliferative T-cell responses were reversible: incubation of tolerized lymph node cells for 5 days in added recombinant (r)IL-2 fully restored proliferative capacity back to normal. We therefore conclude that the main mechanism of i.v.-induced tolerance in our model is anergy of antigen-specific T lymphocytes.
免疫前静脉注射抗原已被证明是在T细胞水平诱导抑制的有效方法。在本研究中，我们证明在免疫前7天静脉注射100微克鸡卵溶菌酶（HEL）可几乎完全抑制关节炎（以抗原诱导的关节炎为模型）。我们研究了其潜在机制，包括CD8 + T淋巴细胞的抑制、辅助性T细胞2（Th2）的抑制或抗原特异性T淋巴细胞的无反应性。用抗CD8或抗白细胞介素-4（IL-4）进行体内治疗并不能消除静脉注射诱导的耐受性。淋巴细胞刺激试验显示，耐受小鼠的抗原特异性增殖反应和IL-2产生减少。通过添加抗IL-4、抗IL-10或抗转化生长因子-β（TGF-β）在体外检测可溶性抑制性细胞因子的可能作用。中和这些因子并不能减少抑制作用。最后，测试了抗原特异性T淋巴细胞的无反应性作为静脉注射诱导耐受性的可能机制。结果表明，T细胞增殖反应的降低是可逆的：在添加重组（r）IL-2的情况下，将耐受的淋巴结细胞孵育5天可使增殖能力完全恢复正常。因此，我们得出结论，在我们的模型中，静脉注射诱导耐受性的主要机制是抗原特异性T淋巴细胞的无反应性。
