Maximus Peto’s Commentary
I wonder what others on this distribution list will make of this report of “widespread” CD4 T cell reactivity to tau in different human populations; I don’t recall this being reported before.
Widespread Tau-Specific CD4 T Cell Reactivity in the General Population.
J Immunol. 2019 Jul 1;203(1):84-92.
Cecilia S Lindestam Arlehamn, John Pham, Roy N Alcalay, April Frazier, Evan Shorr, Chelsea Carpenter, John Sidney, Rekha Dhanwani, Julian Agin-Liebes, Francesca Garretti, Amy W Amara, David G Standaert, Elizabeth J Phillips, Simon A Mallal, Bjoern Peters, David Sulzer, Alessandro Sette
PubMed publication date (edat): 5/16/2019
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.