Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice

Clinical improvement during pregnancy in multiple sclerosis (MS) patients suggests that sex hormones exert potent regulatory effects on autoimmune function. Our previous studies demonstrated that estrogen- (17β-estradiol; E2) mediated protection against experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, hinges on the B cells, leading to elevated numbers of IL-10 secreting CD1d^hiCD5⁺ B regulatory cells (B_regs) in wild type mice. Our data show that co-administration of E2 and IL-10⁺ B cells ameliorates EAE disease severity and limits CNS infiltrating leukocytes in B cell deficient mice. Additionally, treatment with E2 and B_regs reduces demyelination and dramatically decreases the proportion of CD11b⁺CD45^hi activated microglia/macrophages found in the CNS of immunized animals compared to vehicle, E2 or B_reg cells alone. Furthermore, mice given E2 and B_regs exhibit increased numbers of peripheral programmed death-1 positive CD4⁺Foxp3⁺ regulatory T cells (T_regs) and up-regulation of programmed death receptor-ligand-1 and CD80 expression on monocytes. Our study suggests IL-10 producing B_regs have powerful therapeutic potential as an agent against EAE when augmented with E2 treatment.