Early Treatment of Experimental Autoimmune Encephalomyelitis with Cannabidiol Suppresses Tc1 Cells and Reduces Neuroinflammation

Abstract

Abstract Multiple sclerosis (MS) is a neurodegenerative, T cell-mediated, autoimmune disease. In this study, we examined use of the phytocannabinoid, cannabidiol (CBD), in the experimental autoimmune encephalomyelitis (EAE) model to determine CBD’s potential as an oral therapy for MS. We hypothesized that 75mg/kg of oral CBD for 5 days after initiation of disease would reduce EAE severity through suppression of either the early peripheral immune or late neuroimmune response. EAE was induced in C57BL/6 mice at two different magnitudes, and peripheral inflammatory and neuroinflammatory responses were measured at days 3, 10, and 18. Th1, Th17, Tc1, Tc17, Tregs, and myeloid derived suppressor cells (MDSC) were identified in lymph node and spleen by flow cytometry to determine if CBD altered these cell populations in the secondary lymphoid tissues. Additionally, neuroinflammation was identified in brain and spinal cord using hematoxylin and eosin (H&E) and CD3 staining to detect cellular infiltrates and T cells, respectively. Our results show a clear correlation between reduction in the percentage of MOG-35–55 specific Tc1 cells in the spleen at day 10, and reduced neuroinflammation and clinical scores at day 18 in EAE mice treated with CBD; however, this correlation was not seen in the milder form of disease. These results suggest CBD’s ability to reduce neuroinflammation in EAE might be due to early suppression of the Tc1 phenotype in the peripheral inflammatory response, and that CBD’s ability to suppress disease is dependent on the magnitude of the inflammatory response. Furthermore, this study highlights the effectiveness of oral CBD as a treatment for EAE and suggests that CBD might be effective for treatment of other T cell-mediated diseases.