Stem-like precursors of helper T cells dependent on Eomes and Myb sustain CD4+ T cell responses during chronic infection

However, the factors that regulate their maintenance and function in response to protracted infections remain poorly understood. Here, using the Lymphocytic Choriomeningitis Virus (LCMV) model, we identify a transcriptionally defined population of CD4+ helper T cells, which manifest in chronic but not acute infection, to be essential to sustain chronic CD4+ T cell immunity.

These cells, which are distinct from memory-like CD4+ T cells, express markers typically associated with exhausted T cells, including PD-1 and TOX, and can self-renewal and give rise to both type 1 T helper (Th1) and follicular T helper (Tfh) cells, thus acting as precursors of T helper (pTh) cells. These cells also mediate the Th1-biased differentiation and expansion in response to PD-1-targeted immune checkpoint blockade (ICB).