Novel lymphocytic choriomeningitis virus strain sustains abundant exhausted progenitor CD8 T cells without systemic viremia

ABSTRACT: Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and a natural mouse pathogen. LCMV Armstrong, an acutely resolved strain, and LCMV Clone 13, a mutant that establishes chronic infection, have provided contrasting infection models that continue to inform the fundamental biology of T cell differentiation, regulation of exhaustion, and response to checkpoint blockade. Here, we report the isolation and characterization of LCMV Minnesota (LCMV-MN), which was naturally transmitted to laboratory mice upon cohousing with pet shop mice and shares 80-95% amino acid homology with previously characterized LCMV strains. Infection of laboratory mice with purified LCMV-MN resulted in viral persistence that was intermediate between LCMV Armstrong and Clone 13, with widely disseminated viral replication and viremia that was controlled within 15-30 days, unless CD4 T cells were depleted prior to infection. LCMV-MN responding CD8+ T cells biased differentiation towards the recently described PD1+ CXCR5+ Tim-3lo stem-like CD8+ T cell population (also referred to as T exhausted progenitors, Tpex) that effectuates responses to PD-1 blockade checkpoint inhibition, a therapy that rejuvenates responses against chronic infections and cancer. This subset resembled previously characterized PD1+ TCF1+ stem-like CD8+ T cells by transcriptional, phenotypic, and functional assays, yet was atypically abundant. LCMV-MN may provide a tool to better understand the breadth of immune responses in different settings of chronic antigen stimulation as well as the ontogeny of T exhausted progenitors and the regulation of responsiveness to PD-1 blockade.

ORGANISM(S): Mus musculus

PROVIDER: GSE207983 | GEO | 2022/08/22

REPOSITORIES: GEO