Heterogeneity and clonality of kidney-infiltrating T cells in murine lupus nephritis.

ABSTRACT: We previously found that kidney-infiltrating T cells (KITs) in murine lupus nephritis (LN) resembled dysfunctional T cells that infiltrate tumors. This unexpected finding raised the question of how to reconcile the "exhausted" phenotype of KITs with ongoing tissue destruction in LN. To address this, we performed single-cell RNA-Seq and TCR-Seq of KITs in murine lupus models. We found that CD8+ KITs existed first in a transitional state, before clonally expanding and evolving toward exhaustion. On the other hand, CD4+ KITs did not fit into current differentiation paradigms but included both hypoxic and cytotoxic subsets with a pervasive exhaustion signature. Thus, autoimmune nephritis is unlike acute pathogen immunity; rather, the kidney microenvironment suppresses T cells by progressively

SUBMITTER: Smita S 

PROVIDER: S-EPMC9089785 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature