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New study in Science Immunology shows that individuals with Parkinson’s disease exhibit decreased levels of CD8+ memory T cells and fail to generate memory T cells in response to COVID-19 vaccination. This underscores the critical importance of mitochondrial quality control in the formation of CD8+ memory T cells.

The research*, published in Science Immunology , was conducted by Dr Fabien Franco and directed by Pr Ping-Chih Ho , member of the Lausanne Branch of the Ludwig Institute for Cancer Research, in the Oncology department UNIL-CHUV.

Mitophagy, a crucial safeguarding process for maintaining mitochondrial quality, is frequently compromised in human diseases, such as Parkinson's disease. However, its role in adaptive immunity has not been well-understood. Notably, the differentiation and survival of memory CD8+ T cells hinge on oxidative metabolism, which necessitates robust mitochondrial quality control.

The regulatory networks controlling mitophagy work in tandem with mitochondrial dynamics and functional adjustments to safeguard against cell death when memory T cells are being generated.

Furthermore, they discovered that regulators of mitophagy, including Parkin and NIX, were upregulated in response to interleukin-15 (IL-15) to support the formation of memory T cells. Mechanistically, Parkin played a role in suppressing VDAC1-dependent apoptosis in memory T cells. In contrast, NIX expression in T cells countered ferroptosis by preventing metabolic dysfunction resulting from impaired mitophagy. In conclusion, their findings indicate that the mitophagy machinery orchestrates the survival and metabolic dynamics necessary for the formation of memory T cells, highlighting the urgent medical need to restore T cell-mediated protection against viral infections and vaccination challenges in Parkinson's disease patients.

The research was supported by the European Research Council Staring Grant (802773-MitoGuide), Swiss Cancer Foundation, the Cancer Research Institute (Lloyd J. Old STAR award), Helmut Horten Stifung, and Melanoma Research Alliance Established Investigator Award, the Ludwig Institute for Cancer Research, the University of Lausanne (UNIL) and the Department of Oncology (CHUV).

*Regulatory proteins of mitophagy restrict cell death for mounting memory CD8+ T cell formation