024 – Investigating the interaction of Th17 cells and B cells in initiation and progression of EAE
Anna Kolz (1) – Anneli Peters (1)
Institute of Clinical Neuroimmunology, Ludwig-Maximilians-Universität München, Munich, Germany (1)
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Both Th1 and Th17 cells contribute to disease pathogenesis in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Compelling evidence also suggests a pivotal role of B cells in CNS autoimmunity. However, it is only poorly understood how T cells and B cells cooperate to induce disease. Meningeal ectopic lymphoid follicle-like structures (eLFs) in MS and EAE have been hypothesized to fuel chronic inflammation directly in the CNS. To differentiate between Th1- and Th17-driven aspects of disease, we established adoptive transfer EAE. Nave myelin oligodendrocyte glycoprotein (MOG)-specific CD4+ T cells are in vitro differentiated with polarizing cytokines into Th1 or Th17 cells and transferred into wild-type recipient mice. We found that both Th1 and Th17 cells induced EAE with similar severity, and maintained their original cytokine profile also in the inflamed CNS. Importantly, large lymphocytic aggregates were found in association with meninges of brain and spinal cord primarily in Th17 recipients. These follicles contained clusters of T cells and B cells, with fractions of both being positive for the proliferation marker Ki67, and are reminiscent of follicle-like structures that have been described in MS patients. The aim of this study is to investigate whether and how Th17 cells and B cells interact with each other in eLFs. Both Th17 cells and B cells can be labeled with genetically-encoded protein activation sensors which will allow us to study their interactions and possible subsequent activation events in real-time using intravital microscopy of the CNS. Unraveling the special relationship of Th17 cells and B cells in disease pathogenesis may provide targets for therapeutic intervention in MS.