Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8+ tissue-resident memory T cells

Changwei Peng; Matthew A Huggins; Kelsey M Wanhainen; Todd P. Knutson; Hanbin Lu; Hristo Georgiev; Kristen L. Mittelsteadt; Nicholas Jarjour; Haiguang Wang; Kristin A. Hogquist; Daniel J. Campbell; Henrique Borges da Silva; Stephen C. Jameson

doi:10.1016/j.immuni.2021.11.017

Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8⁺ tissue-resident memory T cells

Changwei Peng, Matthew A Huggins, Kelsey M Wanhainen, Todd P. Knutson, Hanbin Lu, Hristo Georgiev, Kristen L. Mittelsteadt, Nicholas Jarjour, Haiguang Wang, Kristin A. Hogquist, Daniel J. Campbell, Henrique Borges da Silva, Stephen C. Jameson

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

13 Scopus citations

Abstract

Elevated gene expression of the costimulatory receptor Icos is a hallmark of CD8⁺ tissue-resident memory (Trm) T cells. Here, we examined the contribution of ICOS in Trm cell differentiation. Upon transfer into WT mice, Icos^−/− CD8⁺ T cells exhibited defective Trm generation but produced recirculating memory populations normally. ICOS deficiency or ICOS-L blockade compromised establishment of CD8⁺ Trm cells but not their maintenance. ICOS ligation during CD8⁺ T cell priming did not determine Trm induction; rather, effector CD8⁺ T cells showed reduced Trm differentiation after seeding into Icosl^−/− mice. Icos^YF/YF CD8⁺ T cells were compromised in Trm generation, indicating a critical role for PI3K signaling. Modest transcriptional changes in the few Icos^−/− Trm cells suggest that ICOS-PI3K signaling primarily enhances the efficiency of CD8⁺ T cell tissue residency. Thus, local ICOS signaling promotes production of Trm cells, providing insight into the contribution of costimulatory signals in the generation of tissue-resident populations.

Original language	English (US)
Pages (from-to)	98-114.e5
Journal	Immunity
Volume	55
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2021.11.017
State	Published - Jan 11 2022

Bibliographical note

Funding Information:
We thank the members of the Jamequist lab for intellectual input. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported. This work was funded by NIH awards to S.C.J. ( R01 AI038903 and AI145147 ). The graphical abstract was created with BioRender.com.

Funding Information:
We thank the members of the Jamequist lab for intellectual input. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported. This work was funded by NIH awards to S.C.J. (R01 AI038903 and AI145147). The graphical abstract was created with BioRender.com. C.P. and S.C.J. conceived the project and designed the experiments. D.J.C. K.A.H. and S.C.J. provided mice and reagents for all experiments. C.P. M.A.H. K.M.W. H.G. K.L.M. N.N.J. H.W. and H.B.d.S. performed the experiments. C.P. H.L. T.P.K. and S.C.J. analyzed the data. C.P. and S.C.J. wrote the manuscript, with input from all authors. The authors declare no competing interests.

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

ICOS
PI3K
resident memory T cells

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2021.11.017

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Peng, C., Huggins, M. A., Wanhainen, K. M., Knutson, T. P., Lu, H., Georgiev, H., Mittelsteadt, K. L., Jarjour, N., Wang, H., Hogquist, K. A., Campbell, D. J., Borges da Silva, H., & Jameson, S. C. (2022). Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8⁺ tissue-resident memory T cells. Immunity, 55(1), 98-114.e5. https://doi.org/10.1016/j.immuni.2021.11.017

Peng, C, Huggins, MA, Wanhainen, KM, Knutson, TP, Lu, H, Georgiev, H, Mittelsteadt, KL, Jarjour, N , Wang, H , Hogquist, KA, Campbell, DJ, Borges da Silva, H & Jameson, SC 2022, 'Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8⁺ tissue-resident memory T cells', Immunity, vol. 55, no. 1, pp. 98-114.e5. https://doi.org/10.1016/j.immuni.2021.11.017

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title = "Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8+ tissue-resident memory T cells",

abstract = "Elevated gene expression of the costimulatory receptor Icos is a hallmark of CD8+ tissue-resident memory (Trm) T cells. Here, we examined the contribution of ICOS in Trm cell differentiation. Upon transfer into WT mice, Icos−/− CD8+ T cells exhibited defective Trm generation but produced recirculating memory populations normally. ICOS deficiency or ICOS-L blockade compromised establishment of CD8+ Trm cells but not their maintenance. ICOS ligation during CD8+ T cell priming did not determine Trm induction; rather, effector CD8+ T cells showed reduced Trm differentiation after seeding into Icosl−/− mice. IcosYF/YF CD8+ T cells were compromised in Trm generation, indicating a critical role for PI3K signaling. Modest transcriptional changes in the few Icos−/− Trm cells suggest that ICOS-PI3K signaling primarily enhances the efficiency of CD8+ T cell tissue residency. Thus, local ICOS signaling promotes production of Trm cells, providing insight into the contribution of costimulatory signals in the generation of tissue-resident populations.",

keywords = "ICOS, PI3K, resident memory T cells",

author = "Changwei Peng and Huggins, {Matthew A} and Wanhainen, {Kelsey M} and Knutson, {Todd P.} and Hanbin Lu and Hristo Georgiev and Mittelsteadt, {Kristen L.} and Nicholas Jarjour and Haiguang Wang and Hogquist, {Kristin A.} and Campbell, {Daniel J.} and {Borges da Silva}, Henrique and Jameson, {Stephen C.}",

note = "Funding Information: We thank the members of the Jamequist lab for intellectual input. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported. This work was funded by NIH awards to S.C.J. ( R01 AI038903 and AI145147 ). The graphical abstract was created with BioRender.com. Funding Information: We thank the members of the Jamequist lab for intellectual input. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported. This work was funded by NIH awards to S.C.J. (R01 AI038903 and AI145147). The graphical abstract was created with BioRender.com. C.P. and S.C.J. conceived the project and designed the experiments. D.J.C. K.A.H. and S.C.J. provided mice and reagents for all experiments. C.P. M.A.H. K.M.W. H.G. K.L.M. N.N.J. H.W. and H.B.d.S. performed the experiments. C.P. H.L. T.P.K. and S.C.J. analyzed the data. C.P. and S.C.J. wrote the manuscript, with input from all authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

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doi = "10.1016/j.immuni.2021.11.017",

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AU - Peng, Changwei

AU - Huggins, Matthew A

AU - Wanhainen, Kelsey M

AU - Knutson, Todd P.

AU - Lu, Hanbin

AU - Georgiev, Hristo

AU - Mittelsteadt, Kristen L.

AU - Jarjour, Nicholas

AU - Wang, Haiguang

AU - Hogquist, Kristin A.

AU - Campbell, Daniel J.

AU - Borges da Silva, Henrique

AU - Jameson, Stephen C.

N1 - Funding Information: We thank the members of the Jamequist lab for intellectual input. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported. This work was funded by NIH awards to S.C.J. ( R01 AI038903 and AI145147 ). The graphical abstract was created with BioRender.com. Funding Information: We thank the members of the Jamequist lab for intellectual input. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported. This work was funded by NIH awards to S.C.J. (R01 AI038903 and AI145147). The graphical abstract was created with BioRender.com. C.P. and S.C.J. conceived the project and designed the experiments. D.J.C. K.A.H. and S.C.J. provided mice and reagents for all experiments. C.P. M.A.H. K.M.W. H.G. K.L.M. N.N.J. H.W. and H.B.d.S. performed the experiments. C.P. H.L. T.P.K. and S.C.J. analyzed the data. C.P. and S.C.J. wrote the manuscript, with input from all authors. The authors declare no competing interests. Publisher Copyright: © 2021 Elsevier Inc.

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N2 - Elevated gene expression of the costimulatory receptor Icos is a hallmark of CD8+ tissue-resident memory (Trm) T cells. Here, we examined the contribution of ICOS in Trm cell differentiation. Upon transfer into WT mice, Icos−/− CD8+ T cells exhibited defective Trm generation but produced recirculating memory populations normally. ICOS deficiency or ICOS-L blockade compromised establishment of CD8+ Trm cells but not their maintenance. ICOS ligation during CD8+ T cell priming did not determine Trm induction; rather, effector CD8+ T cells showed reduced Trm differentiation after seeding into Icosl−/− mice. IcosYF/YF CD8+ T cells were compromised in Trm generation, indicating a critical role for PI3K signaling. Modest transcriptional changes in the few Icos−/− Trm cells suggest that ICOS-PI3K signaling primarily enhances the efficiency of CD8+ T cell tissue residency. Thus, local ICOS signaling promotes production of Trm cells, providing insight into the contribution of costimulatory signals in the generation of tissue-resident populations.

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