CD4+ T cells play a critical role in sustaining the effector function of CD8+ T cells during chronic viral infection. When CD4+ T cell “help” is absent, following transient CD4+ T cell depletion, CD8+ T cells enter a dysfunctional state, losing their capacity for viral control. Here, we applied scRNA-seq to determine the CD4+ T cell subsets that repopulate following transient CD4+ T cell depletion, during LCMV Clone 13 infection. Overall design: CD44+ CD4+ T cells were FACS-sorted from control or CD4+ T cell-depleted mice on day 21 post-LCMV Cl13 infection (2 mice per condition) and were loaded on the Chromium Controller (10x Genomics). Single-cell RNA-seq libraries were prepared using the 10x Genomics Chromium Next GEM Single Cell 5’ Reagent Kits v2 (Dual Index) according to manufacturer’s protocol.