Th136 - T Cell Auto-proliferation in Multiple Sclerosis

Philip De Jager, MD, PhD – Director, Center for Translational and Computational Neuroimmunology, Columbia Medical Center; Hanane Touil, PhD – Post-doc, Center for Translational and Computational Neuroimmunology, Columbia Medical Center

Abstract Text:

Introduction: Multiple sclerosis (MS) is an inflammatory disease characterized by distributed functional changes from MS susceptibility variants across all immune cell types and T and B cell modulation in the clinical setting. Autoproliferation of T cells has been reported as one dysfunctional response in MS. Here, we aim to assess the auto-proliferative capacity of cells from untreated MS patients in comparison to both treated patients and healthy donors. In addition, we are expanding our study to samples from at-risk MS patients' family members to assess for the presence of auto-proliferative phenomena prior to disease onset.

Methods: Cryopreserved PBMCs from untreated and treated MS patients, healthy donors, and at-risk MS patient family members were thawed, stained with CFSE and cultured for 7 days in AIM-V media without activation. PBMCs were collected and stained for CD3, CD4, CD54RA, CD27, HLA-DR, CD20, using multiparametric flow cytometry (LSR II) we T cell proliferation was measured.

Results: Untreated RRMS patient samples have significantly higher frequency of auto-proliferating CD3+CD4+HLA-DR+ T cells than healthy donors. Treatment with Glatiramer Acetate (GA) appears to diminish the auto-proliferation pattern observed in RRMS. The remaining samples are currently being processed and will be presented at the conference.

Conclusion: We have replicated the reported auto-proliferative capacity of T cells in MS. The underlying immune dysfunction for the auto-proliferation appears to be reversible with GA, which has been reported to shift T cell phenotypes and enhance Treg function. We therefore set the stage for a more detailed, mechanistic investigation of autoproliferation in MS.