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 N 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

Immunity. 2022 Jan 11;55(1):98-114.e5. doi: 10.1016/j.immuni.2021.11.017. Epub 2021 Dec 20.

Affiliations

¹ Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
² Minnesota Supercomputing Institute, University of Minnesota, Saint Paul, MN 55108, USA.
³ Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ Benaroya Research Institute and Department of Immunology University of Washington School of Medicine, Seattle, WA 98101, USA.
⁵ Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: james024@umn.edu.

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.

Keywords: ICOS; PI3K; resident memory T cells.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adoptive Transfer
Animals
Antibodies, Blocking / metabolism
CD8-Positive T-Lymphocytes / immunology*
Cell Differentiation
Cells, Cultured
Inducible T-Cell Co-Stimulator Ligand / immunology
Inducible T-Cell Co-Stimulator Ligand / metabolism
Inducible T-Cell Co-Stimulator Protein / genetics
Inducible T-Cell Co-Stimulator Protein / metabolism*
Lymphocyte Activation
Memory T Cells / immunology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphatidylinositol 3-Kinases / metabolism
Signal Transduction

Substances

Antibodies, Blocking
Icos protein, mouse
Icosl protein, mouse
Inducible T-Cell Co-Stimulator Ligand
Inducible T-Cell Co-Stimulator Protein