Changes in CD4+ T cell affinity for MOG do not correlate with symptom relapse or remission in secondary progressive demyelinating disease (P4109)

Abstract

Abstract We investigated the role of CD4 T cell frequency and affinity in the nonobese diabetic (NOD) mouse model of EAE. This model is clinically relevant in its MHC-class II-associated proclivity to autoimmune disease and its tendency to follow a secondary progressive disease course that resembles that seen in the majority of MS patients. Using the NOD model, we quantified the affinity of CD4 T cells for myelin oligodendrocyte glycoprotein (MOG) at initial peak of disease, symptom remission and at chronic disease time points. We used the micropipette adhesion frequency assay to obtain a sensitive and physiologically relevant two dimensional measurement of T-cell receptor affinity for peptide:MHC in a cell-anchored system. This assay allows us to quantify both frequency and affinity of antigen-specific CD4 T cells that are minimally detected by MHC-class II tetramer-based assays. Our data demonstrated that CD4 T cells isolated from the CNS at the initial peak of disease have similar affinities to those isolated at remission and chronic time points. However, CNS-infiltrating Tregs were roughly twice as frequent at disease remission as compared to initial peak of disease (p<0.0001). Additionally, changes in the distribution of cytokine-producing CD4 T cells seemed to contribute to the remission of symptomatic disease. Thus, Treg frequency and effector cytokine profile determined remission and relapse of symptoms and this progression was independent of changes in T cell affinity.