Shi F D, He B, Li H, Matusevicius D, Link H, Ljunggren H G
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Eur J Immunol. 1998 Nov;28(11):3587-93. doi: 10.1002/(SICI)1521-4141(199811)28:11<3587::AID-IMMU3587>3.0.CO;2-Y.
The interactions of CD28-B7 and CD40-CD40 ligand (CD40L) pathways in T cell costimulation and autoimmune disease are incompletely understood. We sought to address this issue by investigation of the genesis of acetylcholine receptor (AChR)-induced antibody-mediated experimental autoimmune myasthenia gravis (EAMG) in CD28- and CD40L-deficient mice (CD28-/-, CD40L-/-). Compared to wild-type mice, the CD28-/- mice became less susceptible, and CD40L-/- mice were completely resistant to EAMG induction. Analysis of T helper functions, reflected by cytokine responses, revealed a switch to a Th1 profile in CD28-/- mice. Consistently, levels of serum AChR-specific antibodies of the IgG1 isotype were decreased in CD28-/- mice. In the CD40L-/- mice, both Th1 and Th2 cytokine responses were diminished, and T cell-dependent AChR-reactive B cell responses were more severely impaired than in the CD28-/- mice. Thus, CD28 and CD40L are differentially required for induction of EAMG.
CD28 - B7和CD40 - CD40配体（CD40L）通路在T细胞共刺激和自身免疫性疾病中的相互作用尚未完全明确。我们试图通过研究乙酰胆碱受体（AChR）诱导的抗体介导的实验性自身免疫性重症肌无力（EAMG）在CD28和CD40L缺陷小鼠（CD28 - / - 、CD40L - / - ）中的发病机制来解决这一问题。与野生型小鼠相比，CD28 - / - 小鼠对EAMG的易感性降低，而CD40L - / - 小鼠对EAMG诱导完全具有抗性。通过细胞因子反应反映的辅助性T细胞功能分析显示，CD28 - / - 小鼠转变为Th1型。一致地，CD28 - / - 小鼠中IgG1同种型的血清AChR特异性抗体水平降低。在CD40L - / - 小鼠中，Th1和Th2细胞因子反应均减弱，且T细胞依赖性AChR反应性B细胞反应比CD28 - / - 小鼠受损更严重。因此，诱导EAMG对CD28和CD40L的需求存在差异。
