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J Immunol. 2019 Jul 1;203(1):84-92. doi: 10.4049/jimmunol.1801506. Epub 2019 May 13.

Widespread Tau-Specific CD4 T Cell Reactivity in the General Population.

Author information

1
Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037.
2
Department of Neurology, Columbia University Irving Medical Center, New York State Psychiatric Institute, New York, NY 10032.
3
Department of Psychiatry, Columbia University Irving Medical Center, New York State Psychiatric Institute, New York, NY 10032.
4
Department of Pharmacology, Columbia University Irving Medical Center, New York State Psychiatric Institute, New York, NY 10032.
5
Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35233.
6
Vanderbilt University School of Medicine, Nashville, TN 37235.
7
Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia 6150, Australia; and.
8
Department of Medicine, University of California, San Diego, La Jolla, CA 92093.
9
Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037; alex@lji.org.

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.

PMID:
31085590
PMCID:
PMC6581570
[Available on 2020-07-01]
DOI:
10.4049/jimmunol.1801506

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