Immunity. 2017 Nov 21;47(5):943-958.e9. doi: 10.1016/j.immuni.2017.10.014. Epub 2017 Nov 14.
Chang, YH; Wang, KC; Chu, KL; Clouthier, DL; Tran, AT; Perez, MS Torres; Zhou, AC; Abdul-Sater, AA; Watts, TH
University of Toronto, Toronto, ON M5S 1A8, Canada.
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs). Mice with hypofunctional GITRL in Lyz2+ cells had decreased LCMV-specific CD4+ T cell accumulation and increased viral load. GITR signals in CD4+ T cells occurred after priming to upregulate OX40, CD25, and chemokine receptor CX3CR1. Thus IFN-I (signal 3) induced a post-priming checkpoint (signal 4) for CD4+ T cell accumulation, revealing a division of labor between cDCs and monocyte-derived APCs in regulating T cell expansion.
The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 350 scientific publications are based on research using Ozgene mice.