Non-pathogenic tissue-resident CD8⁺ T cells uniquely accumulate in the brains of lupus-prone mice.

ABSTRACT: Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8⁺ T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4⁺ cells are predominant. Brain-infiltrating CD8⁺ T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69⁺CD122^-PD1⁺CD44⁺CD62L^-) and expressing adhesion molecules (VLA-4⁺LFA-1⁺) complementary to activated brain endothelium. Remarkably, infiltrating CD8⁺ T cells do not cause tissue damage in lupus-prone mice, as genetic ablation of these cells via ?2?m deficiency does not reverse neuropathology, but exacerbates disease both in the brain and globally despite decreased serum IgG levels. Thus, lupus-associated inflammation disrupts the blood-brain barrier in a discriminating way biased in favor of non-pathogenic CD8⁺ T cells relative to other infiltrating leukocytes, perhaps preventing further tissue damage in such a sensitive organ.

SUBMITTER: Morawski PA 

PROVIDER: S-EPMC5241651 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature