Defining the niche for stem-like CD8 T cell formation and function.

TCF-1 CD8 T cell populations have emerged as critical determinants for long-lived immunological memory. This cell population has stem-like properties and is implicated in improved disease outcomes by driving sustained killing of infected cells and maintaining the immune-cancer equilibrium. During an immune response, several factors, including antigen deposition and affinity, the inflammatory milieu, and T cell priming dynamics, aggregate to skew CD8 T cell differentiation.

Transient inhibition of type I interferon enhances CD8 T cell stemness and vaccine protection.

Unlabelled: Developing vaccines that promote CD8 T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1 stem cell-like memory T (T ) cells are important determinants of long-lived memory. Yet, the developmental requirements for T formation are unclear.

Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet subset normally associated with chronic infection.

Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands.

T cells dynamically interact with multiple, distinct cellular subsets to determine effector and memory differentiation. Here, we developed a platform to quantify cell location in three dimensions to determine the spatial requirements that direct T cell fate. After viral infection, we demonstrated that CD8 effector T cell differentiation is associated with positioning at the lymph node periphery.