Additionally, and similar to CD8+ T cells responding to chronic infection (Wherry et al., 2007), most CD4+ T cell clusters from LCMV Cl13 infection uniformly displayed increased TCR signaling, T cell dysfunction, and T cell exhaustion gene expression profiles (Figure 4F–G, Figure 4—figure supplement 1F), once again suggesting that persistent exposure to antigen and inflammation may result in the upregulation of some conserved (and dysregulated) gene expression programs that span multiple phenotypically distinct CD4+ T cell subsets. Here, CD4 is linked to infection.