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

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

doi:10.1016/j.immuni.2021.11.017

Cited by 60 publications

(45 citation statements)

References 83 publications

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“…5A). Expression of Icos, which encodes inducible T cell costimulator (ICOS) in IST Trm cells is consistent with the recent report that signalling via ICOS generates Trm cells 57 .…”

Section: Subunit Vaccination-induced Cd8 + Trm Cells Express Lineage-...supporting

confidence: 89%

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

Suryadevara

Kumar

Xiang

et al. 2022

Sci Rep

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Natural infection as well as vaccination with live or attenuated viruses elicit tissue resident, CD8+ memory T cell (Trm) response. Trm cells so elicited act quickly upon reencounter with the priming agent to protect the host. These Trm cells express a unique molecular signature driven by the master regulators—Runx3 and Hobit. We previously reported that intranasal instillation of a subunit vaccine in a prime boost vaccination regimen installed quick-acting, CD8+ Trm cells in the lungs that protected against lethal vaccinia virus challenge. It remains unexplored whether CD8+ Trm responses so elicited are driven by a similar molecular signature as those elicited by microbes in a real infection or by live, attenuated pathogens in conventional vaccination. We found that distinct molecular signatures distinguished subunit vaccine-elicited lung interstitial CD8+ Trm cells from subunit vaccine-elicited CD8+ effector memory and splenic memory T cells. Nonetheless, the transcriptome signature of subunit vaccine elicited CD8+ Trm resembled those elicited by virus infection or vaccination. Clues to the basis of tissue residence and function of vaccine specific CD8+ Trm cells were found in transcripts that code for chemokines and chemokine receptors, purinergic receptors, and adhesins when compared to CD8+ effector and splenic memory T cells. Our findings inform the utility of protein-based subunit vaccination for installing CD8+ Trm cells in the lungs to protect against respiratory infectious diseases that plague humankind.

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“…5A). Expression of Icos, which encodes inducible T cell costimulator (ICOS) in IST Trm cells is consistent with the recent report that signalling via ICOS generates Trm cells 57 .…”

Section: Subunit Vaccination-induced Cd8 + Trm Cells Express Lineage-...supporting

confidence: 89%

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

Suryadevara

Kumar

Xiang

et al. 2022

Sci Rep

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“…Blockade of ICOS prolonged graft survival, indicating that ICOS plays a functional role in the presence of CTLA-4 Ig treatment. ICOS has been implicated as an important costimulatory receptor in multiple T cell subsets, and was recently shown to be important for the formation of resident memory CD8 + T cells (Peng et al, 2022). ICOS is attractive as a therapeutic target because it is selectively and transiently upregulated on CD43 + T EFF , and thus represents a potentially selective way to inhibit allogeneic CD8 + T cells during rejection.…”

Section: Discussionmentioning

confidence: 99%

Transplantation Elicits a Clonally Diverse CD8⁺T Cell Response that is Comprised of Potent CD43⁺Effectors

Cohen

Kallarakal

Ibukun

et al. 2022

Preprint

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CD8+ T cells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. After antigen encounter, CD8+ T cells differentiate into effector populations that traffic to allografts and exert cytotoxic functions. The phenotype of effector CD8+ T cells after transplantation is not well-understood. We characterized the use of an allogeneic MHC Class I tetramer comprised of the ubiquitous self-peptide QL9 presented by H-2Ld, to assess anti-donor H-2b CD8+ T cells. T cells specific for this epitope were found at an elevated precursor frequency in naive mice relative to model antigen and viral epitopes. After grafting of allogeneic H-2d skin, Ld QL9+ T cells divided and differentiated into effector CD8+ T cells, but only weakly increased in numbers. Antigen-specific effector CD8+ T cells downregulated CD127, but a low frequency expressed the effector marker KLRG-1. Using high-parameter flow cytometry, we found that expression of the activated glycoform of sialophorin CD43 increased at acute timepoints. Relative to CD43- populations, effector CD43+ CD8+ T cells displayed potent effector phenotype and functionality, including GranzymeB production, cytokine production, and accelerated graft rejection. In the presence of costimulation blockade with CTLA-4 Ig, CD43+ effector T cells maintained high expression of the costimulatory receptor ICOS. ICOS blockade in conjunction with CTLA-4 Ig prolonged graft survival. These data demonstrate that the graft-specific CD8+ T cell response has a distinct response profile relative to anti-pathogen responses and that CD43 and ICOS are critical surface receptors that define potent effector CD8+ T cell populations that form after grafting. These findings have implications for the selective targeting of CD8+ T cells that mediate transplant rejection.

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“…Recently, Peng et al. found that local ICOS signaling also promotes the generation of intestinal T RM by activating the PI3K pathway and downregulating KLF2 expression ( 43 ). While the maintenance of T CM and T EM depends on the presence of IL-15, IL-15 is not necessary for T RM retention ( 44 ).…”

Section: T Rm In the Intestinementioning

confidence: 99%

An Overview of Tissue-Resident Memory T Cells in the Intestine: From Physiological Functions to Pathological Mechanisms

2022

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The human intestine contains a complex network of innate and adaptive immune cells that provide protective immunity. The dysfunction of this network may cause various chronic diseases. A large number of T cells in the human intestine have been identified as tissue-resident memory T cells (TRM). TRM are present in the peripheral tissues, and they do not recirculate through the blood. It is known that TRM provide rapid immune responses at the frontline of pathogen invasion. Recent evidence also suggests that these cells play a role in tumor surveillance and the pathogenesis of autoimmune diseases. In this review, we discuss the general features of intestinal TRM together with their role in intestinal infection, colorectal cancer (CRC), and inflammatory bowel disease (IBD).

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

Cited by 60 publications

References 83 publications

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

Transplantation Elicits a Clonally Diverse CD8⁺T Cell Response that is Comprised of Potent CD43⁺Effectors

An Overview of Tissue-Resident Memory T Cells in the Intestine: From Physiological Functions to Pathological Mechanisms

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

Cited by 60 publications

References 83 publications

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination

Transplantation Elicits a Clonally Diverse CD8+T Cell Response that is Comprised of Potent CD43+Effectors

An Overview of Tissue-Resident Memory T Cells in the Intestine: From Physiological Functions to Pathological Mechanisms

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Transplantation Elicits a Clonally Diverse CD8⁺T Cell Response that is Comprised of Potent CD43⁺Effectors