Enhancement of CD8+ T Cell Responses by ICOS/B7h Costimulation

Wallin, Jeffrey J.; Liang, Linda; Bakardjiev, Anastasia; Sha, William C.

doi:10.4049/jimmunol.167.1.132

Cited by 144 publications

(110 citation statements)

References 32 publications

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“…ICOS costimulation regulates production of multiple cytokines, including IL-4, IL-10, and IFN-␥ (1,4,10,11), and is critical in Ab responses to T-dependent Ags (11)(12)(13)(14)(15). ICOS costimulation regulates effector functions of both Th2 and Th1 cells (16), as well as CD8 ϩ T cells (17,18). Recent studies also implicate ICOS-B7h in maintaining the balance between effector and regulatory T cells in mouse models of asthma (19,20) and autoimmune diabetes (21).…”

Section: Icos-inducedmentioning

confidence: 99%

ICOS-Induced B7h Shedding on B Cells Is Inhibited by TLR7/8 and TLR9

Logue

Bakkour

Murphy

et al. 2006

The Journal of Immunology

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We report in this study that B7h, the ligand for the ICOS costimulatory receptor, is rapidly shed from mouse B cells following either ICOS binding or BCR engagement. Shedding occurs through proteolytic cleavage that releases the extracellular ICOS-binding region of B7h. Prior exposure of B7h-expressing APCs to ICOS-expressing cells inhibits their subsequent ability to costimulate IFN-γ and IL-4 production from CD4+ T cells. Shedding is regulated as TLR7/8 and TLR9 ligands inhibit B7h shedding. A shedding-resistant B7h mutant elicits greater costimulation of IFN-γ production from CD4+ T cells than does wild-type B7h. These data define shedding of B7h as a novel mechanism for controlling costimulatory signaling by B7-CD28 family members that is regulated on B cells by TLR signaling.

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Section: Icos-inducedmentioning

confidence: 99%

ICOS-Induced B7h Shedding on B Cells Is Inhibited by TLR7/8 and TLR9

Logue

Bakkour

Murphy

et al. 2006

The Journal of Immunology

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“…Inducible costimulatory molecule (ICOS) is expressed on activated T cells and has been reported to provide costimulatory signals to CD8 + T cells in vitro (12,25). In vivo studies show that anti-ICOS mAb or ICOSIg prolongs cardiac allograft survival to 21 days compared to 7 days in the control group, but these results were biologically modest given the 14-day treatment strategy (14).…”

Section: Introductionmentioning

confidence: 99%

Targeting LFA-1 Synergizes with CD40/CD40L Blockade for Suppression of Both CD4-Dependent and CD8-Dependent Rejection

Wang

Gao

Lunsford

et al. 2003

American Journal of Transplantation

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Allogeneic hepatocytes elicit CD4-dependent and (CD4-independent) CD8 + T-cell-initiated graft rejection. The (CD4-independent) CD8 + T-cell pathway is resistant to immunosuppressive strategies that readily and indefinitely suppress CD4 + T-cell-dependent rejection responses. Consequently, successful immunoregulation of hepatocyte-initiated immune responses requires a strategy which regulates both CD4-dependent and CD8-dependent rejection responses. Interference with CD40/CD40 ligand (CD40L) costimulation only transiently suppresses CD4-and CD8-dependent hepatocyte rejection. Interference with CD28/B7 costimulation transiently suppresses CD4-dependent hepatocyte rejection, but is ineffective for suppression of CD8-dependent hepatocyte rejection. To date, hepatocyte survival > 60 days post-transplant has not been achieved by any immunotherapeutic strategy. In the current study, we evaluated a novel immunosuppressive strategy which targets both LFA-1 and CD40L-mediated signals. Targeting LFA-1 suppressed (CD4-independent) CD8 + T-cell-initiated hepatocyte rejection such that allogeneic hepatocyte survival > 60 days was achieved in 70% of CD4 KO mice. Targeting both LFA-1-mediated signals and CD40/CD40L costimulation resulted in synergistic effects, such that hepatocellular survival > 60 days was achieved in 100% of C57BL/6 mice (which have both CD4-and CD8-dependent T-cell pathways available).

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“…Several reports indicate that ICOS is not expressed on resting CD8 ϩ T cells and is only slowly up-regulated after activation (3,5,20). It was therefore important to determine whether Listeriaspecific CD8 ϩ T cells express ICOS.…”

Section: Icos Expression On Listeria-specific Cd4 ϩ and Cd8 ϩ T Cellsmentioning

confidence: 99%

“…After activation, CD8 ϩ T cells express ICOS at a low density on their surface (5,20). However, the blocking of ICOS signaling does not affect CD8 ϩ T cell responses to different viral pathogens (16).…”

mentioning

confidence: 99%

“…After treatment of mice with bacterial superantigens, inhibition of ICOS signaling diminishes CD8 ϩ T cell proliferation (21). ICOS costimulation of CD8 ϩ T cells in vitro promotes proliferation and cytokine production (20), and transfection of tumor cells with the ICOS ligand, B7RP-1, accelerates CD8 ϩ T cell-mediated tumor rejection (20,22 Here we analyze the role of ICOS in the acquired immune response to the intracellular bacterium Listeria monocytogenes. Listeria Ags are presented via both the MHC class I and class II pathways.…”

mentioning

confidence: 99%

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Inducible Costimulator Protein Controls the Protective T Cell Response Against Listeria monocytogenes

Mittrücker

Kursar

Köhler

et al. 2002

The Journal of Immunology

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The inducible costimulator protein (ICOS) was recently identified as a costimulatory molecule for T cells. Here we analyze the role of ICOS for the acquired immune response of mice against the intracellular bacterium Listeria monocytogenes. During oral L. monocytogenes infection, low levels of ICOS expression were detected by extracellular and intracellular Ab staining of Listeria-specific CD4+ and CD8+ T cells. Blocking of ICOS signaling with a soluble ICOS-Ig fusion protein markedly impaired the Listeria-specific T cell responses. Compared with control mice, the ICOS-Ig treated mice generated significantly reduced numbers of Listeria-specific CD8+ T cells in spleen and liver, as determined by tetramer and intracellular cytokine staining. In contrast, the specific CD8+ T cell response in the intestinal mucosa did not appear to be impaired by the ICOS-Ig treatment. Analysis of the CD4+ T cell response revealed that ICOS-Ig treatment also affected the specific CD4+ T cell response. When restimulated with listerial Ag in vitro, reduced numbers of CD4+ T cells from infected and ICOS-Ig-treated mice responded with IFN-γ production. The impaired acquired immune response in ICOS-Ig treated mice was accompanied by their increased susceptibility to L. monocytogenes infection. ICOS-Ig treatment drastically enhanced bacterial titers, and a large fraction of mice succumbed to the otherwise sublethal dose of infection. Thus, ICOS costimulation is crucial for protective immunity against the intracellular bacterium L. monocytogenes.

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Enhancement of CD8+ T Cell Responses by ICOS/B7h Costimulation

Cited by 144 publications

References 32 publications

ICOS-Induced B7h Shedding on B Cells Is Inhibited by TLR7/8 and TLR9

ICOS-Induced B7h Shedding on B Cells Is Inhibited by TLR7/8 and TLR9

Targeting LFA-1 Synergizes with CD40/CD40L Blockade for Suppression of Both CD4-Dependent and CD8-Dependent Rejection

Inducible Costimulator Protein Controls the Protective T Cell Response Against Listeria monocytogenes

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