Do Dysfunctional T Cells Predict Parkinson’s Disease?
New research suggests T cells may contribute to Parkinson’s disease
T cells run amok is well understood in autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and inflammatory bowel disease. Recent research by scientists at the La Jolla Institute for Immunology suggests that a similar T cell dysfunction may contribute to Parkinson’s disease.
The lab of LJI Professor Alessandro Sette, Dr.Biol.Sci. found that Parkinson’s patients’ T cells target key proteins called alpha-synuclein and PINK1 in brain cells. Earlier research by the same group identified which subtypes of T cells target alpha-synuclein. But the research didn’t demonstrate a timeline to show when the T cells might be involved in Parkinson’s. This study does.
“We can see these reactive T cells in people after they develop Parkinson’s, but what happens before that?” says LJI Visiting Scientist Emil Johansson, PhD, co-author of the study.
In the new research published in npj Parkinson’s Disease, the investigators found that potentially damaging T cell reactivity is greatest during the “prodromal” period in Parkinson’s, which is years before an actual diagnosis.
“This T cell immunity could be a marker for early Parkinson’s treatment, even before people show symptoms,” says Sette, senior author of the study. “And there’s reason to think that treating Parkinson’s in the very early stages can lead to a better outcome.”
The team studied volunteers at high risk of developing Parkinson’s. The participants had genetic risk factor for Parkinson’s and some had symptoms like disrupted REM sleep cycles and loss of sense of smell, possible early signs of Parkinson’s. Using Flurospot to analyze blood samples from the participants, they found high levels of T cells that reacted to alpha-synuclein or PINK1.
The research found that the potentially damaging T cells appeared early, significantly earlier than onset of noticeable motor symptoms like tremors. T cell reactivity to PINK1 was at its highest prior to diagnosis.
Sette cautions about drawing conclusions from the research because Parkinson’s is a complex disease. The study doesn’t prove the T cells are driving Parkinson’s inflammation.
“Parkinson’s disease is associated with the destruction of nervous system cells,” Sette says. “Does that destruction cause autoimmunity — or is the autoimmunity the cause of the disease? That’s the chicken-and-the-egg of inflammation in Parkinson’s disease.”
Nonetheless, the fact T cell reactivity is greatest when patients are closest to diagnosis is suggestive that there is a connection. It could potentially lead to early diagnostic tools, for example.
LJI researchers are studying ways to block inflammation and protect brain cells. Some T cells help control inflammation, so they plan to further study the role T cells play in Parkinson’s and other neurodegenerative diseases.
Sette notes, “We are very interested in diseases such as Alzheimer’s, for example, where a lot of progress has been made toward identifying people in very early stages of the disease progression.”