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

• DOI: 10.1038/srep40838
• Publication Date: 2017-01-18T10:28:36Z
• Authors: Peter A. Morawski; Chen-Feng Qi; Silvia Bolland
• Keywords: CD4-Positive T-Lymphocytes; Central Nervous System; 0303 health sciences; Brain; Mice, Transgenic; CD8-Positive T-Lymphocytes; Article; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Phenotype; Antigens, CD; Blood-Brain Barrier; Toll-Like Receptor 8; Animals; Cytokines; Lupus Erythematosus, Systemic; Cell Adhesion Molecules; Transcription Factors

AbstractSevere 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 β2 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.