title: 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 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.
authors.affiliation: Laboratory of Immunogenetics, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Morawski
authors.affiliation: Laboratory of Immunogenetics, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
authors.forename: Chen-Feng
authors.initials: CF
authors.lastname: Qi
authors.affiliation: Laboratory of Immunogenetics, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolland
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D051200:Toll-Like Receptor 8 / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D051200:Toll-Like Receptor 8; D014157:Transcription Factors