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

Area of Science:

• Neuroimmunology
• Proteinopathy Research

Background:

• Aggregated and hyperphosphorylated tau (p-tau) are implicated in various neurologic disorders, including Parkinson disease (PD).
• While not traditionally considered autoimmune, tau aggregates might activate the immune system.

Purpose of the Study:

• To investigate T cell responses to tau and p-tau peptides in PD patients and healthy controls.
• To determine if T cell responses to tau are modulated by age or PD.

Main Methods:

• Comparison of T cell responses to tau and p-tau-derived peptides.
• Analysis of CD4+ T cell responses and cytokine secretion (IFN-γ, IL-5, IL-4).
• Inclusion of PD patients, age-matched controls, and young healthy controls.

Main Results:

• All groups showed CD4+ T cell responses to tau peptides, secreting IFN-γ, IL-5, and/or IL-4.
• Similar magnitude and breadth of T cell responses were observed in PD patients and controls.
• Certain tau-derived epitopes were more prevalent in PD participants, indicating potential immune system activation.

Conclusions:

• T cells recognizing tau epitopes are present in significant numbers, bypassing central and peripheral tolerance.
• Age and PD disease do not appear to significantly alter the magnitude or nature of these T cell responses to tau.