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

Barbara Altendorfer; Michael Stefan Unger; Rodolphe Poupardin; Anna Hoog; Daniela Asslaber; Iris Karina Gratz; Heike Mrowetz; Ariane Benedetti; Diana Marisa Bessa de Sousa; Richard Greil; Alexander Egle; David Gate; Tony Wyss-Coray; Ludwig Aigner

doi:10.4049/jimmunol.2100737

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

Barbara Altendorfer, Michael Stefan Unger, Rodolphe Poupardin, Anna Hoog, Daniela Asslaber, Iris Karina Gratz, Heike Mrowetz, Ariane Benedetti, Diana Marisa Bessa de Sousa, Richard Greil, Alexander Egle, David Gate, Tony Wyss-Coray, Ludwig Aigner^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1-14
Number of pages	14
Journal	Journal of Immunology
Volume	209
Issue number	7
DOIs	https://doi.org/10.4049/jimmunol.2100737
State	Published - Oct 1 2022

Funding

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. 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.

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.4049/jimmunol.2100737

Cite this

Altendorfer, B., Unger, M. S., Poupardin, R., Hoog, A., Asslaber, D., Gratz, I. K., Mrowetz, H., Benedetti, A., de Sousa, D. M. B., Greil, R., Egle, A., Gate, D., Wyss-Coray, T., & Aigner, L. (2022). Transcriptomic Profiling Identifies CD8⁺ T Cells in the Brain of Aged and Alzheimer's Disease Transgenic Mice as Tissue-Resident Memory T Cells. Journal of Immunology, 209(7), 1-14. https://doi.org/10.4049/jimmunol.2100737

@article{f4392df392ab44eeae7f921bd723df52,

title = "Transcriptomic Profiling Identifies CD8+ T Cells in the Brain of Aged and Alzheimer's Disease Transgenic Mice as Tissue-Resident Memory T Cells",

abstract = "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.",

author = "Barbara Altendorfer and Unger, {Michael Stefan} and Rodolphe Poupardin and Anna Hoog and Daniela Asslaber and Gratz, {Iris Karina} and Heike Mrowetz and Ariane Benedetti and {de Sousa}, {Diana Marisa Bessa} and Richard Greil and Alexander Egle and David Gate and Tony Wyss-Coray and Ludwig Aigner",

note = "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: {\textcopyright} 2022 by The American Association of Immunologists, Inc.",

year = "2022",

month = oct,

day = "1",

doi = "10.4049/jimmunol.2100737",

language = "English (US)",

volume = "209",

pages = "1--14",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "7",

}

Altendorfer, B, Unger, MS, Poupardin, R, Hoog, A, Asslaber, D, Gratz, IK, Mrowetz, H, Benedetti, A, de Sousa, DMB, Greil, R, Egle, A, Gate, D, Wyss-Coray, T & Aigner, L 2022, 'Transcriptomic Profiling Identifies CD8⁺ T Cells in the Brain of Aged and Alzheimer's Disease Transgenic Mice as Tissue-Resident Memory T Cells', Journal of Immunology, vol. 209, no. 7, pp. 1-14. https://doi.org/10.4049/jimmunol.2100737

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 -