A pro-inflammatory effector-memory T cell program links peripheral EBV priming to CNS autoimmunity
- 1University Hospital Erlangen
Abstract
T and B cell-mediated immunosurveillance of the central nervous system (CNS) can become maladaptive in multiple sclerosis (MS). Epstein-Barr virus (EBV) is a likely driver of MS, yet how exactly EBV-specific T cells contribute remains unclear. We generated an antigen-resolved atlas of blood and cerebrospinal fluid (CSF) T cells from untreated MS patients and controls. T cell clones carrying a GZMK effector-memory program in blood were CSF-biased, particularly in MS, and associated with EBV reactivity. In CSF, EBV-reactive GZMK CD8 T cells engaged B lineage cells. Activated CD8 T cells promoted atypical B cell and plasmablast formation, whereas GZMK-enriched effector-memory cells induced IL-6 and IL-8 release from myeloid cells. Together, these findings identify an infection-imprinted, CNS-biased state and support a model in which EBV-specific CD8 T cells contribute to inflammation through a non-canonical mode of B cell and myeloid cell activation.
Related
- IL-23 licenses the transition from preclinical autoimmunity to inflammatory arthritis through IL-17A-dependent mechanisms
- Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration
- Dysbiosis-induced expansion of AXL-positive inflammatory type 3 dendritic cells triggers preclinical autoimmunity
- Themis controls T cell activation, effector functions, and metabolism of peripheral CD8+ T cells
- Glucocorticoid receptor modulation as a host-directed strategy for inflammatory priming across chronic disease states
BibTeX
@misc{kristensen2026proinflammatory,
title = {{A pro-inflammatory effector-memory T cell program links peripheral EBV priming to CNS autoimmunity}},
author = {N. P. Kristensen and T. Tsaktanis and S. Frischholz and J. K. Benotmane and L. Klotz and P. Hilgendorf and M. Grotz and M. Sousa and L. F. Voss and S. Schattgen and V. Lang and H. Reimann and C. Storr and R. Lang and B. Spriewald and F. B. Engel and M. Boettcher and D. Mougiakakos and S. Schreiber and D. H. Heiland and S. Mader and P. G. Thomas and S. R. Hadrup and V. Rothhammer and K. Schober},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.753741},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.753741v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A pro-inflammatory effector-memory T cell program links peripheral EBV priming to CNS autoimmunity
AU - N. P. Kristensen
AU - T. Tsaktanis
AU - S. Frischholz
AU - J. K. Benotmane
AU - L. Klotz
AU - P. Hilgendorf
AU - M. Grotz
AU - M. Sousa
AU - L. F. Voss
AU - S. Schattgen
AU - V. Lang
AU - H. Reimann
AU - C. Storr
AU - R. Lang
AU - B. Spriewald
AU - F. B. Engel
AU - M. Boettcher
AU - D. Mougiakakos
AU - S. Schreiber
AU - D. H. Heiland
AU - S. Mader
AU - P. G. Thomas
AU - S. R. Hadrup
AU - V. Rothhammer
AU - K. Schober
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.753741
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.753741v1
AB - T and B cell-mediated immunosurveillance of the central nervous system (CNS) can become maladaptive in multiple sclerosis (MS). Epstein-Barr virus (EBV) is a likely driver of MS, yet how exactly EBV-specific T cells contribute remains unclear. We generated an antigen-resolved atlas of blood and cerebrospinal fluid (CSF) T cells from untreated MS patients and controls. T cell clones carrying a GZMK effector-memory program in blood were CSF-biased, particularly in MS, and associated with EBV reactivity. In CSF, EBV-reactive GZMK CD8 T cells engaged B lineage cells. Activated CD8 T cells promoted atypical B cell and plasmablast formation, whereas GZMK-enriched effector-memory cells induced IL-6 and IL-8 release from myeloid cells. Together, these findings identify an infection-imprinted, CNS-biased state and support a model in which EBV-specific CD8 T cells contribute to inflammation through a non-canonical mode of B cell and myeloid cell activation.
ER -