Therapeutic recombinant immune complexes (rICs) inhibit T cell recruitment to the spinal cord during Experimental Autoimmune Encephalomyelitis (EAE)

Abstract

Abstract Multiple sclerosis (MS) is an autoimmune neurodegenerative disease mediated by autoreactive Th1 and Th17 cells that migrate into the central nervous system (CNS) and target myelin proteins ultimately leading to neuronal damage. Current immunomodulatory treatments reduce disease severity but do not cure the disease, and they do not work for all patients. Recombinant ICs recapitulate the anti-inflammatory properties of intravenous immunoglobulin and may be a viable therapy for MS. The objective of our study was to determine if a rIC, M019, could inhibit autoreactive T cell recruitment into the CNS using the EAE model. To demonstrate that M019 could inhibit disease severity when given therapeutically, C57BL/6 mice were immunized with a CFA-MOG 35–55emulsion followed by pertussis toxin to induce EAE. Upon symptom development, mice were randomly assigned to either the vehicle or M019 treatment groups and treated with M019 or vehicle daily. Mice treated with M019 exhibited reduced clinical scores and lethality compared to vehicle treated mice. Flow cytometric analysis of T cell infiltration into the CNS revealed that M019 inhibited CD4 +and CD8 +T cell infiltration compared to vehicle treated mice with EAE. However, spleen cells from M019 treated mice had similar levels of Th17 cells and increased Th1 cells compared to the vehicle treated group. These results suggest that M019 is not inhibiting Th17 responses in the periphery but is inhibiting their recruitment into the CNS. The effect of M019 is likely indirect, as in vivo drug binding studies show that M019 binds strongly to monocytes with low level binding to T cells. Our studies suggest that M019 may be an effective therapeutic for MS patients.