Journal article
Widespread Tau-Specific CD4 T Cell Reactivity in the General Population
The Journal of Immunology, Vol.203(1), pp.84-92
2019
Abstract
Tau protein is found to be aggregated and hyperphosphorylated (p-tau) in many neurologic disorders, including Parkinson disease (PD) and related parkinsonisms, Alzheimer disease, traumatic brain injury, and even in normal aging. Although not known to produce autoimmune responses, we hypothesized that the appearance of aggregated tau and p-tau with disease could activate the immune system. We thus compared T cell responses to tau and p-tau–derived peptides between PD patients, age-matched healthy controls, and young healthy controls (<35 y old; who are less likely to have high levels of tau aggregates). All groups exhibited CD4+ T cell responses to tau-derived peptides, which were associated with secretion of IFN-γ, IL-5, and/or IL-4. The PD and control participants exhibited a similar magnitude and breadth of responses. Some tau-derived epitopes, consisting of both unmodified and p-tau residues, were more highly represented in PD participants. These results were verified in an independent set of PD and control donors (either age-matched or young controls). Thus, T cells recognizing tau epitopes escape central and peripheral tolerance in relatively high numbers, and the magnitude and nature of these responses are not modulated by age or PD disease.
Details
- Title
- Widespread Tau-Specific CD4 T Cell Reactivity in the General Population
- Authors/Creators
- C.S. Lindestam Arlehamn (Author/Creator)J. Pham (Author/Creator) - La Jolla Institute for ImmunologyR.N. Alcalay (Author/Creator) - Columbia UniversityA. Frazier (Author/Creator) - La Jolla Institute for ImmunologyE. Shorr (Author/Creator) - Columbia UniversityC. Carpenter (Author/Creator) - La Jolla Institute for ImmunologyJ. Sidney (Author/Creator) - La Jolla Institute for ImmunologyR. Dhanwani (Author/Creator) - La Jolla Institute for ImmunologyJ. Agin-Liebes (Author/Creator) - Columbia UniversityF. Garretti (Author/Creator) - Columbia UniversityA.W. Amara (Author/Creator) - University of Alabama at BirminghamD.G. Standaert (Author/Creator) - University of Alabama at BirminghamE.J. Phillips (Author/Creator) - Murdoch UniversityS.A. Mallal (Author/Creator) - Murdoch UniversityB. Peters (Author/Creator) - La Jolla Institute for ImmunologyD. Sulzer (Author/Creator) - Columbia UniversityA. Sette (Author/Creator) - University of California San Diego
- Publication Details
- The Journal of Immunology, Vol.203(1), pp.84-92
- Publisher
- American Association of Immunologists
- Identifiers
- 991005541555007891
- Copyright
- © 2019 by The American Association of Immunologists, Inc.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.67 Parkinson's Disease
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology