Richards Amanda L, Kapp Linda M, Wang Xiaohong, Howie Heather L, Hudson Krystalyn E
Bloodworks Northwest Research Institute , Seattle, WA , USA.
Front Immunol. 2016 Sep 19;7:348. doi: 10.3389/fimmu.2016.00348. eCollection 2016.
Autoimmune hemolytic anemia (AIHA) occurs when pathogenic autoantibodies against red blood cell (RBC) antigens are generated. While the basic disease pathology of AIHA is well studied, the underlying mechanism(s) behind the failure in tolerance to RBC autoantigens are poorly understood. Thus, to investigate the tolerance mechanisms required for the establishment and maintenance of tolerance to RBC antigens, we developed a novel murine model. With this model, we evaluated the role of regulatory T cells (Tregs) in tolerance to RBC-specific antigens. Herein, we show that neither sustained depletion of Tregs nor immunization with RBC-specific proteins in conjunction with Treg depletion led to RBC-specific autoantibody generation. Thus, these studies demonstrate that Tregs are not required to prevent autoantibodies to RBCs and suggest that other tolerance mechanisms are likely involved.
自身免疫性溶血性贫血（AIHA）是在针对红细胞（RBC）抗原的致病性自身抗体产生时发生的。虽然AIHA的基本疾病病理学已得到充分研究，但对红细胞自身抗原耐受失败背后的潜在机制了解甚少。因此，为了研究建立和维持对红细胞抗原耐受性所需的耐受机制，我们开发了一种新型小鼠模型。利用该模型，我们评估了调节性T细胞（Tregs）在对红细胞特异性抗原的耐受性中的作用。在此，我们表明，无论是Tregs的持续耗竭，还是与Treg耗竭联合使用红细胞特异性蛋白进行免疫，都不会导致红细胞特异性自身抗体的产生。因此，这些研究表明，Tregs并非预防针对红细胞的自身抗体所必需的，并提示可能涉及其他耐受机制。
