“…PD-1 checkpoint blockade is a highly effective immune therapeutic that re-activates exhausted CD8 T cells during persistent infection (Barber et al, 2006;Hashimoto et al, 2018) and across a variety of cancers (Sharma et al, 2021;Wei et al, 2017). Despite their nonexhausted state, TFH cells (Ansel et al, 1999;Fazilleau et al, 2009;Vinuesa et al, 2005) and their follicular regulatory counterpart (TFR) (Gonzalez-Figueroa et al, 2021;Linterman et al, 2011;Wu et al, 2020) both express PD-1 with highest levels on GC localized subsets (Haynes et al, 2007;Shulman et al, 2013). Genetic ablation of PD-1 results in increased TFH and TFR cell expansion following immunization (Good-Jacobson et al, 2010;Hams et al, 2011;Sage et al, 2013), in the gut (Kawamoto et al, 2012) and in autoimmune models (Nishimura et al, 1999;Nishimura et al, 2001).…”