Single cell RNA sequencing of the progeny of PD1hi vs PD1low TCF-1+ P14 precursor cells on day 15 after secondary host infection with LCMV Armstrong [scRNA-Seq BD Rhapsody]

ABSTRACT: T-cell exhaustion limits effector T-cell function in chronic infection and tumors. The development of these hypofunctional T-cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T-cell populations in the early phase of acute infections. At that stage early developing TCF1+ precursor population shows an unexpected diversity, which includes precursors of normal memory T-cells but also cells with a phenotype, gene-expression, and epigenetic profile that resembles precursors of exhausted T-cells found in chronic infections. We demonstrate that high ligand affinity promotes, and PD-1 signaling restricts the development of these precursors. While these exhausted precursors are initially frequently found, they decline without being completely lost in infections the immune system resolves. We therefore concluded that precursor T-cells with at least two distinct phenotypes are preemptively generated irrespectively of the outcome of the infection. Here, using adoptively transferred P14 cells, these subsets were isolated early during infection, re-transfered into new hosts that were subsequently infected as well. The entire progeny of the re-transfered cells was analyzed on day 15 pi.

ORGANISM(S): Mus musculus

PROVIDER: GSE278806 | GEO | 2025/02/21

REPOSITORIES: GEO