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Catherine Ann M Gavile, Amanda Alexander, Fred Adler, Brian D Evavold, Antigen dose affects disease kinetics in a murine model of demyelinating disease, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 180.7, https://doi.org/10.4049/jimmunol.202.Supp.180.7
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Abstract
Multiple sclerosis is an autoimmune disorder caused by immune cell damage to the myelin sheath lining nerve cells, leading to neuronal damage and dysfunction. The murine model of the disease - experimental autoimmune encephalomyelitis (EAE) - is induced by inoculation with MOG (myelin oligodendrocyte glycoprotein) peptide and an adjuvant, leading to recapitulation of disease that is mediated primarily by CD4 T cells. In this study, we look at the effect of MOG dosage on demyelinating disease kinetics in WT and MOG-deficient animals, as MOG-deficient mice have different numbers of MOG specific CD4 Teff and Tregs. The T cells from MOG deficient animals have a higher affinity for MOG, expand faster, and cause exacerbated disease in an adoptive transfer model compared to CD4 T cells from wildtype mice. Our results indicate that the dose of MOG peptide used to induce disease can also modulate disease course. Using tenfold lower doses changes T cell and disease kinetics resulting in disease that resolves compared to controls. Taken together, we can use varying doses of MOG as a tool to probe CD8 and CD4 T cell expansion and monitor migration of immune cells to the CNS. Further understanding of the cellular tides during disease course enables us to gain insight on how cell ratios in different sites contribute to disease pathogenesis. Using this information, we are developing mathematical modeling tools that could be used to analyze and predict disease progression.
