Speaker
Description
Maike Hartlehnert (1), David Schafflick (1), Tobias Lautwein (1), Jan-Kolja Strecker (1), Tanja Kuhlmann (2), Heinz Wiendl (1), Gerd Meyer zu Horste (1)
(1) Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany; (2) Institute of Neuropathology, University Hospital Münster, Münster, Germany.
T follicular helper (TFH) cells are a CD4+ T cell subset homing to germinal centres (GCs) of secondary lymphoid organs. Here, TFH cells play a crucial role during the maturation of B lineage cells in physiological immune responses. Pathological structures, morphologically similar to GCs called ectopic lymphoid tissue, can develop in the meninges of multiple sclerosis (MS) patients and correlate with MS severity.
We here speculated that TFH cells interact with B cells in a ‘pathological GC reaction’ locally in the meninges and may promote MS pathology.
We induced the experimental autoimmune encephalomyelitis (EAE) animal model of MS in TFH cell-deficient (CD4CreBcl6flox/flox) mice and found the severity of MOG35-55 peptide induced EAE decreased compared to controls. This correlated with a significantly reduced amount of pathogenic T cells and total B cells infiltrating in the central nervous system (CNS) of TFH-cell deficient mice. To further characterize these B cells in the CNS, we performed transcriptomic profiling.
We also performed an adoptive transfer (AT) EAE using MOG-specific T cells derived from TFH-cell deficient mice transgenically expressing a MOG-specific T cell receptor and their wildtype littermates. We found abundant GC-like ectopic lymphoid tissue in the spinal cord in these mice and CD4CreBcl6flox/flox myelin-reactive T cells induced less severe AT-EAE than wildtype-derived T cells. We are further characterizing ectopic lymphoid tissue to understand local T/B-cell interaction in this model.
Taken together, our data suggest that TFH cells contribute to CNS autoimmunity and exacerbate B cell infiltration in the CNS.
