Schuldt Nathaniel J, Auger Jennifer L, Spanier Justin A, Martinov Tijana, Breed Elise R, Fife Brian T, Hogquist Kristin A, Binstadt Bryce A
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455.
Center for Immunology, University of Minnesota, Minneapolis, MN 55455.
J Immunol. 2017 Jul 1;199(1):33-38. doi: 10.4049/jimmunol.1700406. Epub 2017 May 24.
Despite accounting for 10-30% of the T cell population in mice and humans, the role of dual TCR-expressing T cells in immunity remains poorly understood. It has been hypothesized that dual TCR T cells pose an autoimmune hazard by allowing self-reactive TCRs to escape thymic selection. We revisited this hypothesis using the NOD murine model of type 1 diabetes. We bred NOD mice hemizygous at both TCRα and β (TCRα β) loci, rendering them incapable of producing dual TCR T cells. We found that the lack of dual TCRα expression skewed the insulin-specific thymocyte population toward greater regulatory T (T) cell commitment, resulting in a more tolerogenic T to conventional T cell ratio and protection from diabetes. These data support a novel hypothesis by which dual TCR expression can promote autoimmunity by limiting agonist selection of self-reactive thymocytes into the T cell lineage.
尽管在小鼠和人类的T细胞群体中占10% - 30%，但双TCR表达T细胞在免疫中的作用仍知之甚少。有人推测，双TCR T细胞可能通过使自身反应性TCR逃避胸腺选择而构成自身免疫风险。我们利用1型糖尿病的NOD小鼠模型重新审视了这一假设。我们培育了在TCRα和β（TCRαβ）位点均为半合子的NOD小鼠，使其无法产生双TCR T细胞。我们发现，缺乏双TCRα表达会使胰岛素特异性胸腺细胞群体向更多的调节性T（Treg）细胞分化，导致Treg与常规T细胞的比例更具耐受性，并预防糖尿病。这些数据支持了一个新的假设，即双TCR表达可能通过限制自身反应性胸腺细胞作为激动剂被选择进入T细胞谱系而促进自身免疫。
