Reciprocal modulation of CD4 T cell responses by intravenous immunoglobulin in experimental autoimmune encephalomyelitis (P5178)

Abstract

Abstract IVIg is increasingly used for therapy in many autoimmune and inflammatory diseases; however the mechanisms underlying its therapeutic benefit have remained uncertain. We have investigated the mechanisms in the context of modulation of regulatory and pathogenic CD4 T cells in EAE, a murine model of multiple sclerosis. We demonstrate that IVIg delays the onset of EAE by inhibiting encephalitogenic CD4 T cell subsets (Th1 and Th17 cells) and concomitantly expanding foxp3+ regulatory T cells. Furthermore, IVIg renders effector T cells less pathogenic by decreasing the expression of encephalitogenic molecules such as GM-CSF and podoplanin. Intriguingly and contrary to the current arguments, the inhibitory FcγRIIB and sialylation on IgG are dispensable and F(ab’)2 fragments retained this function of IVIg. Additionally, IVIg sequestered effector T cells into the draining lymph nodes leading to decreased infiltration into CNS. IVIg interfered with S1P-S1P1-mTOR pathway to sequester lymphocytes in the draining lymph nodes and reciprocally regulate CD4 T cell subsets. Our study reveals a novel role of immunoglobulins in modulating polarization, pathogenicity and trafficking of T lymphocytes accounting for the observed beneficial effect during IVIg therapy.