Peer-reviewedCC BY-NC-ND 4.0Nature Neuroscience
Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration
13 affiliations
- 1Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA
- 2Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA
- 3Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
- 4Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
- 5Center for Brain Immunology and Glia (BIG), Washington University School of Medicine, St Louis, MO, USA
- 6Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
- 7Bursky Center for Human Immunology, Washington University School of Medicine, St. Louis, MO, USA
- 8McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
- 9Needleman Center for Neurometabolism and Axonal Therapeutics, St. Louis, MO, USA
- 10Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
- 11Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA. [email protected]
- 12Center for Brain Immunology and Glia (BIG), Washington University School of Medicine, St Louis, MO, USA. [email protected]
- 13Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA. [email protected]
Abstract
Alzheimer’s disease and primary tauopathies are marked by changes in adaptive immunity, with increased brain CD8+ T cells correlating with tau pathology severity. However, how peripheral T cells get primed to enter the brain and contribute to tau-mediated neurodegeneration remains unclear. In different disease conditions, conventional type 1 dendritic cells (cDC1s) cross-present antigens to prime CD8+ T cells into effector cells. We show that tauopathy mice lacking cDC1s or antigen cross-presentation are protected from neurodegeneration, with reduced brain CD8+ T cell infiltration and glial activation. The remaining CD8+ T cells exhibit limited clonal expansion, consistent with impaired priming. We further demonstrate that brain-derived antigens are presented in secondary lymphoid tissues, suggesting a site of T cell activation. Together, these findings establish cDC1-dependent peripheral priming as a key driver of CD8+ T cell accumulation in the brain and tau-mediated neurodegeneration.
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BibTeX
@article{hu2026priming,
title = {{Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration}},
author = {Hao Hu and Peter Bor‐Chian Lin and Carisa Zeng and Yongyi Li and Megan E. Bosch and Joshua T. Emmerson and Prabal Sharma and Ray A. Ohara and Wendy Dong and Tong Wu and Siling Du and Wenqing Gao and Hong Jiang and Liya Yuan and Xin Bao and Shasha Li and Anthony N. Vomund and Petra Erdmann-Gilmore and Yichen Gu and Miwei Hu and Jonathan Nulman and Timothy M. Miller and Wayne M. Yokoyama and Cheryl F. Lichti and Jeffrey Milbrandt and Richard J. Perrin and Jonathan Kipnis and Maxim N. Artyomov and KENNETH M. M. MURPHY and Jason D. Ulrich and David M. Holtzman},
journal = {Nature Neuroscience},
year = {2026},
month = sep,
doi = {10.1038/s41593-026-02427-5},
url = {https://doi.org/10.1038/s41593-026-02427-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration
AU - Hao Hu
AU - Peter Bor‐Chian Lin
AU - Carisa Zeng
AU - Yongyi Li
AU - Megan E. Bosch
AU - Joshua T. Emmerson
AU - Prabal Sharma
AU - Ray A. Ohara
AU - Wendy Dong
AU - Tong Wu
AU - Siling Du
AU - Wenqing Gao
AU - Hong Jiang
AU - Liya Yuan
AU - Xin Bao
AU - Shasha Li
AU - Anthony N. Vomund
AU - Petra Erdmann-Gilmore
AU - Yichen Gu
AU - Miwei Hu
AU - Jonathan Nulman
AU - Timothy M. Miller
AU - Wayne M. Yokoyama
AU - Cheryl F. Lichti
AU - Jeffrey Milbrandt
AU - Richard J. Perrin
AU - Jonathan Kipnis
AU - Maxim N. Artyomov
AU - KENNETH M. M. MURPHY
AU - Jason D. Ulrich
AU - David M. Holtzman
PY - 2026
DA - 2026/09/03
JO - Nature Neuroscience
DO - 10.1038/s41593-026-02427-5
UR - https://doi.org/10.1038/s41593-026-02427-5
AB - Alzheimer’s disease and primary tauopathies are marked by changes in adaptive immunity, with increased brain CD8+ T cells correlating with tau pathology severity. However, how peripheral T cells get primed to enter the brain and contribute to tau-mediated neurodegeneration remains unclear. In different disease conditions, conventional type 1 dendritic cells (cDC1s) cross-present antigens to prime CD8+ T cells into effector cells. We show that tauopathy mice lacking cDC1s or antigen cross-presentation are protected from neurodegeneration, with reduced brain CD8+ T cell infiltration and glial activation. The remaining CD8+ T cells exhibit limited clonal expansion, consistent with impaired priming. We further demonstrate that brain-derived antigens are presented in secondary lymphoid tissues, suggesting a site of T cell activation. Together, these findings establish cDC1-dependent peripheral priming as a key driver of CD8+ T cell accumulation in the brain and tau-mediated neurodegeneration.
SN - 1097-6256
SN - 1546-1726
ER -