TY - JOUR
T1 - Transcriptomic Profiling Identifies CD8+ T Cells in the Brain of Aged and Alzheimer's Disease Transgenic Mice as Tissue-Resident Memory T Cells
AU - Altendorfer, Barbara
AU - Unger, Michael Stefan
AU - Poupardin, Rodolphe
AU - Hoog, Anna
AU - Asslaber, Daniela
AU - Gratz, Iris Karina
AU - Mrowetz, Heike
AU - Benedetti, Ariane
AU - de Sousa, Diana Marisa Bessa
AU - Greil, Richard
AU - Egle, Alexander
AU - Gate, David
AU - Wyss-Coray, Tony
AU - Aigner, Ludwig
N1 - Funding Information:
This work was supported by the PMU FFF Research Fund (E-20/32/169-UNG) and by the Austrian Science Fund FWF Project P 35417-B. The funding bodies did not influence the design of the study and collection, analysis, interpretation of data, or writing of the manuscript.
Funding Information:
This work was supported by the PMU FFF Research Fund (E-20/32/169-UNG) and by the Austrian Science Fund FWF Project P 35417-B. The funding bodies did not influence the design of the study and collection, analysis, interpretation of data, or writing of the manuscript. We thank the flow cytometry and microscopy core facility of Spinal Cord Injury and Tissue Regeneration Center Salzburg. Furthermore, we thank Sabine Bernegger for proofreading the manuscript.
Publisher Copyright:
© 2022 by The American Association of Immunologists, Inc.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Peripheral immune cell infiltration into the brain is a prominent feature in aging and various neurodegenerative diseases such as Alzheimer's disease (AD). As AD progresses, CD8+ T cells infiltrate into the brain parenchyma, where they tightly associate with neurons and microglia. The functional properties of CD8+ T cells in the brain are largely unknown. To gain further insights into the putative functions of CD8+ T cells in the brain, we explored and compared the transcriptomic profile of CD8+ T cells isolated from the brain and blood of transgenic AD (APPswe/PSEN1dE9, line 85 [APP-PS1]) and age-matched wild-type (WT) mice. Brain CD8+ T cells of APP-PS1 and WT animals had similar transcriptomic profiles and substantially differed from blood circulating CD8+ T cells. 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. Furthermore, brain CD8+ T cells of APP-PS1 and aged WT mice showed similar differentially regulated genes as brain Trm CD8+ T cells in mouse models with acute virus infection, chronic parasite infection, and tumor growth. In conclusion, our profiling of brain CD8+ T cells suggests that in AD, these cells exhibit similar adaptive immune responses as in other inflammatory diseases of the CNS, potentially opening the door for immunotherapy in AD. The Journal of Immunology, 2022, 209: 1-14.
AB - Peripheral immune cell infiltration into the brain is a prominent feature in aging and various neurodegenerative diseases such as Alzheimer's disease (AD). As AD progresses, CD8+ T cells infiltrate into the brain parenchyma, where they tightly associate with neurons and microglia. The functional properties of CD8+ T cells in the brain are largely unknown. To gain further insights into the putative functions of CD8+ T cells in the brain, we explored and compared the transcriptomic profile of CD8+ T cells isolated from the brain and blood of transgenic AD (APPswe/PSEN1dE9, line 85 [APP-PS1]) and age-matched wild-type (WT) mice. Brain CD8+ T cells of APP-PS1 and WT animals had similar transcriptomic profiles and substantially differed from blood circulating CD8+ T cells. 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. Furthermore, brain CD8+ T cells of APP-PS1 and aged WT mice showed similar differentially regulated genes as brain Trm CD8+ T cells in mouse models with acute virus infection, chronic parasite infection, and tumor growth. In conclusion, our profiling of brain CD8+ T cells suggests that in AD, these cells exhibit similar adaptive immune responses as in other inflammatory diseases of the CNS, potentially opening the door for immunotherapy in AD. The Journal of Immunology, 2022, 209: 1-14.
UR - http://www.scopus.com/inward/record.url?scp=85139116861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85139116861&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.2100737
DO - 10.4049/jimmunol.2100737
M3 - Article
C2 - 36165202
AN - SCOPUS:85139116861
SN - 0022-1767
VL - 209
SP - 1
EP - 14
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -