New clues suggest how destructive immune cells wreak havoc in the brain
- Thread starter Jaybee00
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Jonathan Edwards
Senior Member (Voting Rights)
CD8 T cells wander into any tissue that is unhappy. I doubt that Tau overexpressing mice tell us much about the processes that cause damage in Alzheimer's. So I am not sure this tells us much. I don't know why it talks about neck lymph nodes because T cells there would have to go back in to the circulation and by chance end up in the brain with some blood going up the carotid.
This has all the hallmarks of immunobabble to me.
This has all the hallmarks of immunobabble to me.
The paper is —
Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration
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.
Web | DOI | PDF | Nature Neuroscience | Open Access
Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration
Hu, Hao; Lin, Peter Bor-Chian; Zeng, Carisa; Li, Yongyi; Bosch, Megan E; Emmerson, Joshua T; Sharma, Prabal; Ohara, Ray A; Dong, Wendy; Wu, Tong; Du, Siling; Gao, Wenqing; Jiang, Hong; Yuan, Liya; Bao, Xin; Li, Shasha; Vomund, Anthony N; Erdmann-Gilmore, Petra; Gu, Yichen; Hu, Miwei; Nulman, Jonathan; Miller, Timothy M; Yokoyama, Wayne M; Lichti, Cheryl F; Milbrandt, Jeffrey; Perrin, Richard J; Kipnis, Jonathan; Artyomov, Maxim N; Murphy, Kenneth M; Ulrich, Jason D; Holtzman, David M
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.
Web | DOI | PDF | Nature Neuroscience | Open Access