Choroid Plexus–Infiltrating T Cells as Drivers of Murine Neuropsychiatric Lupus. Issue 11 (21st September 2022)

• Record Type: Journal Article
• Authors: Moore, Erica; Huang, Michelle W.; Reynolds, Cara A.; Macian, Fernando; Putterman, Chaim
• Is Part Of: Arthritis & rheumatology. Volume 74:Issue 11(2022)
• Page Start: 1796
• Page End: 1807
• Publication Date: 2022-09-21
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.42252
• Languages: English
• ISSNs: 2326-5191

Abstract

Abstract : Objective: T cells are critical in the pathogenesis of systemic lupus erythematosus (SLE) in that they secrete inflammatory cytokines, help autoantibody production, and form autoreactive memory T cells. Although the contribution of T cells to several forms of organ‐mediated damage in SLE has been previously demonstrated, the role of T cells in neuropsychiatric SLE (NPSLE), which involves diffuse central nervous system manifestations and is observed in 20–40% of SLE patients, is not known. Therefore, we conducted this study to evaluate how behavioral deficits are altered after depletion or transfer of T cells, to directly assess the role of T cells in NPSLE. Methods: MRL/ lpr mice, an NPSLE mouse model, were either systemically depleted of CD4+ T cells or intracerebroventricularly injected with choroid plexus (CP)–infiltrating T cells and subsequently evaluated for alterations in neuropsychiatric manifestations. Our study end points included evaluation of systemic disease and assessment of central nervous system changes. Results: Systemic depletion of CD4+ T cells ameliorated systemic disease and cognitive deficits. Intracerebroventricular injection of CP–infiltrating T cells exacerbated depressive‐like behavior and worsened cognition in recipient mice compared with mice who received injection of splenic lupus T cells or phosphate buffered saline. Moreover, we observed enhanced activation in CP–infiltrating T cells when cocultured with brain lysate–pulsed dendritic cells in comparison to the activation levels observed in cocultures with splenic T cells. Conclusion: T cells, and more specifically CP–infiltrating antigen‐specific T cells, contributed to the pathogenesis of NPSLE in mice, indicating that, in the development of more targeted treatments for NPSLE, modulation of T cells may represent a potential therapeutic strategy.