Transcriptomic Proﬁling Identiﬁes CD8+ T Cells in the Brain of Aged and Alzheimer’s Disease Transgenic Mice as Tissue-Resident Memory T Cells

The Journal of Immunology, 2022 · DOI: 10.4049/jimmunol.2100737 · Published: September 15, 2022

Simple Explanation

This study investigates the role of CD8+ T cells in the brains of aged and Alzheimer's disease (AD) transgenic mice. It aims to understand the function of these immune cells in the context of neurodegeneration. The researchers compared the transcriptomic profile of CD8+ T cells isolated from the brain and blood of transgenic AD mice and age-matched wild-type mice. This comparison helps identify unique characteristics of brain-resident CD8+ T cells. The study found that brain CD8+ T cells in both AD and wild-type mice share similar transcriptomic profiles, which are distinct from those of CD8+ T cells circulating in the blood. This suggests that brain CD8+ T cells have a specialized function within the brain tissue.

Study Duration

Not specified

Participants

Transgenic AD (APPswe/PSEN1dE9, line 85 [APP-PS1]) and age-matched wild-type (WT) mice

Evidence Level

Not specified

Key Findings

1
Brain CD8+ T cells in both AD transgenic and aged wild-type mice exhibit a gene signature characteristic of tissue-resident memory (Trm) T cells.
2
The gene signature of brain CD8+ T cells identified them as tissue-resident memory (Trm) T cells. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis on the significantly upregulated genes revealed overrepresentation of biological processes involved in IFN-b signaling and the response to viral infections.
3
Brain CD8+ T cells from both AD and aged wild-type mice show similar differentially regulated genes as brain Trm CD8+ T cells in mouse models with acute virus infection, chronic parasite infection, and tumor growth.

Research Summary

The study explores the transcriptomic profile of CD8+ T cells in the brains of aged and Alzheimer's disease (AD) transgenic mice, comparing them to CD8+ T cells in the blood and identifying them as tissue-resident memory (Trm) T cells. Key findings indicate that brain CD8+ T cells in AD and aged mice share a similar gene signature, distinct from blood CD8+ T cells, and exhibit upregulated genes involved in IFN-b signaling and response to viral infections, suggesting an adaptive immune response in the CNS. Comparative analysis reveals that brain CD8+ T cells in AD and aged mice have similar gene regulation patterns as brain Trm CD8+ T cells in models of viral infection, parasite infection, and tumor growth, implying a common inflammatory response in the CNS.

Practical Implications

Potential Immunotherapeutic Targets

The identification of brain CD8+ T cells as Trm cells expressing IFN-related genes suggests potential immunotherapeutic targets for modulating the immune response in AD.

Understanding AD Pathogenesis

Characterizing the role of CD8+ T cells in AD pathogenesis could lead to a better understanding of the disease mechanisms and the development of new therapeutic strategies.

Comparison to other CNS diseases

The similarity of brain CD8+ T cells in AD to those in other CNS inflammatory diseases may reveal common pathways amenable to therapeutic intervention.

Study Limitations

1
The study is limited to transgenic mouse models of AD, which may not fully reflect the complexity of human AD.
2
The functional consequences of the identified gene signature in brain CD8+ T cells require further investigation.
3
The specific antigens driving the T cell response in the brain of AD mice remain unknown.

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