iScience ( IF 4.6 ) Pub Date : 2020-11-24 , DOI: 10.1016/j.isci.2020.101854 Anastasiia A. Kalinina , Ludmila N. Nesterenko , Alexandra V. Bruter , Denis V. Balunets , Dmitriy M. Chudakov , Mark Izraelson , Olga V. Britanova , Ludmila M. Khromykh , Dmitry B. Kazansky
Complications after vaccination, lack of vaccines against certain infections, and the emergence of antibiotic-resistant microorganisms point to the need for alternative ways of protection and treatment of infectious diseases. Here, we proposed a therapeutic approach to control salmonellosis based on adoptive cell therapy. We showed that the T cell receptor (TCR) repertoire of salmonella-specific memory cells contains 20% of TCR variants with the dominant-active α-chain. Transduction of intact T lymphocytes with the dominant salmonella-specific TCRα led to their enhanced in vitro proliferation in response to salmonella. Adoptive transfer of transduced T cells resulted in a significant decrease in bacterial loads in mice infected with salmonella before or after the adoptive transfer. We demonstrated that adoptive immunotherapy based on T cells, transduced with dominant-specific TCRα could be successfully applied for treatment and prevention of infectious diseases and represent a useful addition to vaccination and existing therapeutic strategies.
中文翻译:
基于链中心TCR的过继免疫治疗感染性疾病
接种疫苗后的并发症,缺乏针对某些感染的疫苗以及出现抗生素抗性微生物,这表明需要保护和治疗传染病的替代方法。在这里,我们提出了一种基于过继细胞疗法控制沙门氏菌病的治疗方法。我们发现沙门氏菌的TCR组成部分-特定记忆细胞包含20%具有显性活性α链的TCR变体。用占优势的沙门氏菌特异性TCRα转导完整的T淋巴细胞导致其响应沙门氏菌的体外增殖增强。在过继转移之前或之后,转导的T细胞的过继转移导致感染沙门氏菌的小鼠的细菌负荷显着降低。我们证明了基于T细胞的过继免疫疗法,