Distinct T cell signatures define subsets of multiple sclerosis patients

Abstract

Abstract Studies of the frequencies of myelin-specific T cells in peripheral blood mononuclear cells (PBMCs) from MS patients compared to healthy controls (HCs) have varied in their results, but no previous work has considered the potential influence of lesion localization on these frequencies. While the majority of relapse-remitting MS (RRMS) patients have lesions localized predominantly in the brain, a subset of RRMS patients (~5%) has neuroinflammation localized predominantly in the spinal cord. Importantly, spinal cord localized lesions are associated with a worse prognosis for patients due to their effect on motor function. Animal models of MS suggest that distinct T cell effector functions correlate with brain versus spinal cord lesions. Therefore, we analyzed PBMCs from MS patients with lesions predominantly in the brain or predominantly in the spinal cord and HCs using ELISPOT to assess the frequency of IFN-γ+ and IL-17+ cells responding to two myelin antigens, myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG). Significant differences in T cell frequencies were determined in some, but not all, comparisons, with MBP-specific IFN-γ+ frequencies showing the greatest separation between our three groups. Strikingly, combining the IFN-γ+ and IL-17+ responses to both MBP and MOG using logistic regression defined distinct T cell signatures that distinguished MS patients with predominantly brain versus predominantly spinal cord lesions. Collectively, this suggests that different myelin-specific T cell responses may influence neuroinflammatory patterns in RRMS patients. Such patterns of peripheral T cell responses may be useful in generating more tailored therapies for patients with MS.