Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation

J. Adam Best; David A. Blair; Jamie Knell; Edward Yang; Viveka Mayya; Andrew Doedens; Michael L. Dustin; Ananda W. Goldrath; Paul Monach; Susan A. Shinton; Richard R. Hardy; Radu Jianu; David Koller; Jim Collins; Roi Gazit; Brian S. Garrison; Derrick J. Rossi; Kavitha Narayan; Katelyn Sylvia; Joonsoo Kang; Anne Fletcher; Kutlu Elpek; Angelique Bellemare-Pelletier; Deepali Malhotra; Shannon Turley; J. Adam Best; Vladimir Jojic; Daphne Koller; Tal Shay; Aviv Regev; Nadia Cohen; Patrick Brennan; Michael Brenner; Taras Kreslavsky; Natalie A. Bezman; Joseph C. Sun; Charlie C. Kim; Lewis L. Lanier; Jennifer Miller; Brian Brown; Miriam Merad; Emmanuel L. Gautier; Claudia Jakubzick; Gwendalyn J. Randolph; Francis Kim; Tata Nageswara Rao; Amy Wagers; Tracy Heng; Michio Painter; Jeffrey Ericson; Scott Davis; Ayla Ergun; Michael Mingueneau; Diane Mathis; Christophe Benoist

doi:10.1038/ni.2536

Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation

J. Adam Best, David A. Blair, Jamie Knell, Edward Yang, Viveka Mayya, Andrew Doedens, Michael L. Dustin, Ananda W. Goldrath, Paul Monach, Susan A. Shinton, Richard R. Hardy, Radu Jianu, David Koller, Jim Collins, Roi Gazit, Brian S. Garrison, Derrick J. Rossi, Kavitha Narayan, Katelyn Sylvia, Joonsoo KangAnne Fletcher, Kutlu Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon Turley, J. Adam Best, Vladimir Jojic, Daphne Koller, Tal Shay, Aviv Regev, Nadia Cohen, Patrick Brennan, Michael Brenner, Taras Kreslavsky, Natalie A. Bezman, Joseph C. Sun, Charlie C. Kim, Lewis L. Lanier, Jennifer Miller, Brian Brown, Miriam Merad, Emmanuel L. Gautier, Claudia Jakubzick, Gwendalyn J. Randolph, Francis Kim, Tata Nageswara Rao, Amy Wagers, Tracy Heng, Michio Painter, Jeffrey Ericson, Scott Davis, Ayla Ergun, Michael Mingueneau, Diane Mathis, Christophe Benoist

Medical School - Twin Cities Campus

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

247 Scopus citations

Abstract

After infection, many factors coordinate the population expansion and differentiation of CD8⁺ effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8⁺ T cell transcriptome throughout infection to establish gene-expression signatures and identify putative transcriptional regulators. Notably, we found that the expression of key gene signatures can be used to predict the memory-precursor potential of CD8⁺ effector cells. Long-lived memory CD8⁺ cells ultimately expressed a small subset of genes shared by natural killer T and γδ T cells. Although distinct inflammatory milieu and T cell precursor frequencies influenced the differentiation of CD8⁺ effector and memory populations, core transcriptional signatures were regulated similarly, whether polyclonal or transgenic, and whether responding to bacterial or viral model pathogens. Our results provide insights into the transcriptional regulation that influence memory formation and CD8⁺ T cell immunity.

Original language	English (US)
Pages (from-to)	404-412
Number of pages	9
Journal	Nature immunology
Volume	14
Issue number	4
DOIs	https://doi.org/10.1038/ni.2536
State	Published - Apr 2013

Bibliographical note

Funding Information:
We thank eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Supported by the US National Institutes of Health (AI072117 and AI067545 to A.W.G.; T32 AI060536 to J.A.B.; PN2 EY016586 to D.A.B. and M.L.D.; P30 CA016087 for cell sorting; and R24 AI072073 (National Institute of Allergy and Infectious Diseases) to the ImmGen Consortium), the Pew Scholars program (A.W.G.) and the Cancer Research Institute (A.W.G. and V.M.).

Publisher link

10.1038/ni.2536

Find It

Find It at U of M Libraries

Cite this

Best, J. A., Blair, D. A., Knell, J., Yang, E., Mayya, V., Doedens, A., Dustin, M. L., Goldrath, A. W., Monach, P., Shinton, S. A., Hardy, R. R., Jianu, R., Koller, D., Collins, J., Gazit, R., Garrison, B. S., Rossi, D. J., Narayan, K., Sylvia, K., ... Benoist, C. (2013). Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation. Nature immunology, 14(4), 404-412. https://doi.org/10.1038/ni.2536

Best, JA, Blair, DA, Knell, J, Yang, E, Mayya, V, Doedens, A, Dustin, ML, Goldrath, AW, Monach, P, Shinton, SA, Hardy, RR, Jianu, R, Koller, D, Collins, J, Gazit, R, Garrison, BS, Rossi, DJ, Narayan, K, Sylvia, K, Kang, J, Fletcher, A, Elpek, K, Bellemare-Pelletier, A, Malhotra, D, Turley, S, Best, JA, Jojic, V, Koller, D, Shay, T, Regev, A, Cohen, N, Brennan, P, Brenner, M, Kreslavsky, T, Bezman, NA, Sun, JC, Kim, CC, Lanier, LL, Miller, J, Brown, B, Merad, M, Gautier, EL, Jakubzick, C, Randolph, GJ, Kim, F, Rao, TN, Wagers, A, Heng, T, Painter, M, Ericson, J, Davis, S, Ergun, A, Mingueneau, M, Mathis, D & Benoist, C 2013, 'Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation', Nature immunology, vol. 14, no. 4, pp. 404-412. https://doi.org/10.1038/ni.2536

@article{a6064fcf86bd4f5d9410d221c677a390,

title = "Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation",

abstract = "After infection, many factors coordinate the population expansion and differentiation of CD8+ effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8+ T cell transcriptome throughout infection to establish gene-expression signatures and identify putative transcriptional regulators. Notably, we found that the expression of key gene signatures can be used to predict the memory-precursor potential of CD8+ effector cells. Long-lived memory CD8+ cells ultimately expressed a small subset of genes shared by natural killer T and γδ T cells. Although distinct inflammatory milieu and T cell precursor frequencies influenced the differentiation of CD8+ effector and memory populations, core transcriptional signatures were regulated similarly, whether polyclonal or transgenic, and whether responding to bacterial or viral model pathogens. Our results provide insights into the transcriptional regulation that influence memory formation and CD8+ T cell immunity.",

author = "Best, {J. Adam} and Blair, {David A.} and Jamie Knell and Edward Yang and Viveka Mayya and Andrew Doedens and Dustin, {Michael L.} and Goldrath, {Ananda W.} and Paul Monach and Shinton, {Susan A.} and Hardy, {Richard R.} and Radu Jianu and David Koller and Jim Collins and Roi Gazit and Garrison, {Brian S.} and Rossi, {Derrick J.} and Kavitha Narayan and Katelyn Sylvia and Joonsoo Kang and Anne Fletcher and Kutlu Elpek and Angelique Bellemare-Pelletier and Deepali Malhotra and Shannon Turley and Best, {J. Adam} and Vladimir Jojic and Daphne Koller and Tal Shay and Aviv Regev and Nadia Cohen and Patrick Brennan and Michael Brenner and Taras Kreslavsky and Bezman, {Natalie A.} and Sun, {Joseph C.} and Kim, {Charlie C.} and Lanier, {Lewis L.} and Jennifer Miller and Brian Brown and Miriam Merad and Gautier, {Emmanuel L.} and Claudia Jakubzick and Randolph, {Gwendalyn J.} and Francis Kim and Rao, {Tata Nageswara} and Amy Wagers and Tracy Heng and Michio Painter and Jeffrey Ericson and Scott Davis and Ayla Ergun and Michael Mingueneau and Diane Mathis and Christophe Benoist",

note = "Funding Information: We thank eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Supported by the US National Institutes of Health (AI072117 and AI067545 to A.W.G.; T32 AI060536 to J.A.B.; PN2 EY016586 to D.A.B. and M.L.D.; P30 CA016087 for cell sorting; and R24 AI072073 (National Institute of Allergy and Infectious Diseases) to the ImmGen Consortium), the Pew Scholars program (A.W.G.) and the Cancer Research Institute (A.W.G. and V.M.).",

year = "2013",

month = apr,

doi = "10.1038/ni.2536",

language = "English (US)",

volume = "14",

pages = "404--412",

journal = "Nature immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation

AU - Best, J. Adam

AU - Blair, David A.

AU - Knell, Jamie

AU - Yang, Edward

AU - Mayya, Viveka

AU - Doedens, Andrew

AU - Dustin, Michael L.

AU - Goldrath, Ananda W.

AU - Monach, Paul

AU - Shinton, Susan A.

AU - Hardy, Richard R.

AU - Jianu, Radu

AU - Koller, David

AU - Collins, Jim

AU - Gazit, Roi

AU - Garrison, Brian S.

AU - Rossi, Derrick J.

AU - Narayan, Kavitha

AU - Sylvia, Katelyn

AU - Kang, Joonsoo

AU - Fletcher, Anne

AU - Elpek, Kutlu

AU - Bellemare-Pelletier, Angelique

AU - Malhotra, Deepali

AU - Turley, Shannon

AU - Best, J. Adam

AU - Jojic, Vladimir

AU - Koller, Daphne

AU - Shay, Tal

AU - Regev, Aviv

AU - Cohen, Nadia

AU - Brennan, Patrick

AU - Brenner, Michael

AU - Kreslavsky, Taras

AU - Bezman, Natalie A.

AU - Sun, Joseph C.

AU - Kim, Charlie C.

AU - Lanier, Lewis L.

AU - Miller, Jennifer

AU - Brown, Brian

AU - Merad, Miriam

AU - Gautier, Emmanuel L.

AU - Jakubzick, Claudia

AU - Randolph, Gwendalyn J.

AU - Kim, Francis

AU - Rao, Tata Nageswara

AU - Wagers, Amy

AU - Heng, Tracy

AU - Painter, Michio

AU - Ericson, Jeffrey

AU - Davis, Scott

AU - Ergun, Ayla

AU - Mingueneau, Michael

AU - Mathis, Diane

AU - Benoist, Christophe

N1 - Funding Information: We thank eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Supported by the US National Institutes of Health (AI072117 and AI067545 to A.W.G.; T32 AI060536 to J.A.B.; PN2 EY016586 to D.A.B. and M.L.D.; P30 CA016087 for cell sorting; and R24 AI072073 (National Institute of Allergy and Infectious Diseases) to the ImmGen Consortium), the Pew Scholars program (A.W.G.) and the Cancer Research Institute (A.W.G. and V.M.).

PY - 2013/4

Y1 - 2013/4

N2 - After infection, many factors coordinate the population expansion and differentiation of CD8+ effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8+ T cell transcriptome throughout infection to establish gene-expression signatures and identify putative transcriptional regulators. Notably, we found that the expression of key gene signatures can be used to predict the memory-precursor potential of CD8+ effector cells. Long-lived memory CD8+ cells ultimately expressed a small subset of genes shared by natural killer T and γδ T cells. Although distinct inflammatory milieu and T cell precursor frequencies influenced the differentiation of CD8+ effector and memory populations, core transcriptional signatures were regulated similarly, whether polyclonal or transgenic, and whether responding to bacterial or viral model pathogens. Our results provide insights into the transcriptional regulation that influence memory formation and CD8+ T cell immunity.

AB - After infection, many factors coordinate the population expansion and differentiation of CD8+ effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8+ T cell transcriptome throughout infection to establish gene-expression signatures and identify putative transcriptional regulators. Notably, we found that the expression of key gene signatures can be used to predict the memory-precursor potential of CD8+ effector cells. Long-lived memory CD8+ cells ultimately expressed a small subset of genes shared by natural killer T and γδ T cells. Although distinct inflammatory milieu and T cell precursor frequencies influenced the differentiation of CD8+ effector and memory populations, core transcriptional signatures were regulated similarly, whether polyclonal or transgenic, and whether responding to bacterial or viral model pathogens. Our results provide insights into the transcriptional regulation that influence memory formation and CD8+ T cell immunity.

UR - http://www.scopus.com/inward/record.url?scp=84875448616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875448616&partnerID=8YFLogxK

U2 - 10.1038/ni.2536

DO - 10.1038/ni.2536

M3 - Article

C2 - 23396170

AN - SCOPUS:84875448616

SN - 1529-2908

VL - 14

SP - 404

EP - 412

JO - Nature immunology

JF - Nature immunology

IS - 4

ER -

Transcriptional insights into the CD8 + T cell response to infection and memory T cell formation

Abstract

Bibliographical note

Publisher link

Find It

Other files and links

Fingerprint

Cite this