The pathogenic role of choroid plexus infiltrating T cells in Neuropsychiatric Lupus

Abstract

Abstract Neuropsychiatric systemic lupus erythematosus (NPSLE) manifests as a range of symptoms, including cognitive abnormalities, mood disorders, and psychosis. The pathogenesis is complex and not yet completely understood. We recently proposed that the choroid plexus (CP) could be an alternative entry site to the blood brain barrier for immune mediators to enter the central nervous system. In the MRL/lpr lupus mouse model, the CP is heavily infiltrated with T and B cells, which is reminiscent of human NPSLE patients whose autopsies revealed infiltrates in the CP. Nevertheless, the role of CP infiltrating T cells in the pathogenesis is not known and is the objective for this study. In two cohorts, we evaluated whether intracerebroventricularly (ICV) delivered MRL/lpr CP T cells accelerate neuropsychiatric disease in young female MRL/lpr mice. Six week old female MRL/lpr mice were injected with MRL/lpr CP CD3+ T cells, MRL/lpr splenic CD3+ T cells, or PBS. The T cells were pooled from the CP and spleen of 16 week old MRL/lpr mice and expanded with anti-CD3/CD28 antibodies (1 ug/mL) and mIL-2 (10 U/mL) for 4 days. About ~200,000 cells were injected into the lateral ventricle from the bregma at AP −0.34 mm, ML −1.0 mm, and depth −2.0 mm. After 4 weeks post-injection, we found that CP T cell recipient mice had increased cognitive deficits compared to PBS controls. Histological assessment revealed an increase in lymphocytic infiltration, the number of proliferating cells, and IgG and complement deposition, in the choroid plexus of CP T recipient mice. Our result indicate that T cells can migrate to and proliferate in the CP following ICV injection, and that brain infiltrating MRL/lpr T cells may be a key contributor to the pathogenesis of NPSLE.