Frontiers in Immunology ( IF 5.7 ) Pub Date : 2021-09-24 , DOI: 10.3389/fimmu.2021.714842 Chitavi D Maulloo 1 , Shijie Cao 1 , Elyse A Watkins 1 , Michal M Raczy 1 , Ani S Solanki 2 , Mindy Nguyen 1 , Joseph W Reda 1 , Ha-Na Shim 1 , D Scott Wilson 1, 3 , Melody A Swartz 1, 4, 5, 6 , Jeffrey A Hubbell 1, 4, 6
Inverse vaccines that tolerogenically target antigens to antigen-presenting cells (APCs) offer promise in prevention of immunity to allergens and protein drugs and treatment of autoimmunity. We have previously shown that targeting hepatic APCs through intravenous injection of synthetically glycosylated antigen leads to effective induction of antigen-specific immunological tolerance. Here, we demonstrate that targeting these glycoconjugates to lymph node (LN) APCs under homeostatic conditions leads to local and increased accumulation in the LNs compared to unmodified antigen and induces a tolerogenic state both locally and systemically. Subcutaneous administration directs the polymeric glycoconjugate to the draining LN, where the glycoconjugated antigen generates robust antigen-specific CD4+ and CD8+ T cell tolerance and hypo-responsiveness to antigenic challenge
中文翻译:
淋巴结靶向合成糖基化抗原导致抗原特异性免疫耐受
将抗原耐受性地靶向抗原呈递细胞 (APC) 的反向疫苗有望预防过敏原和蛋白质药物的免疫以及治疗自身免疫。我们之前已经证明,通过静脉注射合成糖基化抗原靶向肝 APC 可以有效诱导抗原特异性免疫耐受。在这里,我们证明,与未修饰的抗原相比,在稳态条件下将这些糖缀合物靶向淋巴结(LN)APC会导致LN中局部积累和增加,并诱导局部和全身的耐受状态。皮下给药将聚合糖缀合物引导至引流淋巴结,其中糖缀合物抗原产生强大的抗原特异性 CD4 +和 CD8 + T 细胞耐受性以及对抗原攻击的低反应性