B7-H1 Determines Accumulation and Deletion of Intrahepatic CD8+ T Lymphocytes

Dong, Haidong; Zhu, Gefeng; Tamada, Koji; Flies, Dallas B.; Deursen, Jan M. A. van; Chen, Lieping

doi:10.1016/s1074-7613(04)00050-0

Cited by 350 publications

(317 citation statements)

References 45 publications

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“…Depending on the model system, PD-L1 and PD-L2 were initially reported to have inhibitory or stimulatory effects on T cell responses (13,14). Recent reports on PD-L1 using knockout mice or in vivo studies with blocking anti-PD-L1 mAbs have been consistent with an inhibitory role for PD-L1 (13,16,(21)(22)(23)(24)(25)(26). Recent reports on PD-L2 using knockout mice or blocking mAbs still find opposing functions (27,28).…”

Section: Pd-1:pd-l1 Interactionsmentioning

confidence: 99%

PD-1:PD-L1 Interactions Contribute to the Functional Suppression of Virus-Specific CD8+ T Lymphocytes in the Liver

Maier

Isogawa

Freeman

et al. 2007

The Journal of Immunology

214

172

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Mechanisms contributing to the development of chronic viral infections, including chronic hepatitis B virus (HBV) infections, are not well understood. We have shown recently that production of IFN-γ, an important antiviral cytokine, by HBV-specific CTLs is rapidly induced when they enter the liver of HBV transgenic mice, and then rapidly suppressed, despite the continued presence of Ag. Suppression of IFN-γ production by the CTLs coincides with the up-regulation of programmed cell death (PD)-1, a cell surface signaling molecule known to inhibit T cell function. To determine whether PD-1 plays a role in the functional suppression of IFN-γ secretion by CTLs, we treated HBV transgenic mice with blocking Abs specific for PD ligand (PD-L)1, the most widely expressed PD-1 ligand, and adoptively transferred HBV-specific CTLs. Treatment with anti-PD-L1 Abs resulted in a delay in the suppression of IFN-γ-producing CTLs and a concomitant increase in the absolute number of IFN-γ-producing CTLs in the liver. These results indicate that PD-1:PD-L1 interactions contribute to the suppression of IFN-γ secretion observed following Ag recognition in the liver. Blockade of inhibitory pathways such as PD-1:PD-L1 may reverse viral persistence and chronic infection in cases in which the CTL response is suppressed by this mechanism.

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Section: Pd-1:pd-l1 Interactionsmentioning

confidence: 99%

PD-1:PD-L1 Interactions Contribute to the Functional Suppression of Virus-Specific CD8+ T Lymphocytes in the Liver

Maier

Isogawa

Freeman

et al. 2007

The Journal of Immunology

214

172

View full text Add to dashboard Cite

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“…PD1 then transmits elevated negative signals into T cells, which, in collaboration with unregulated inflammatory cytokines (such as TNF and IFNγ), may effectively establish exhaustion, anergy, and subsequent suppression and apoptosis of these cells 40,41,43 . Indeed, we have previously shown that B7-H1 not only controls CD8 + T-cell homeostasis, but also contributes selectively to the deletion of intra hepatic CD8 + T cells 44 . Iwai et al also showed correlatively that PD1-deficient mice were more resistant to acute hepatic damage owing to adenovirus infection 45 .…”

Section: Anergymentioning

confidence: 99%

“…That little or no immune response to the virus is observed in humans and non-human primates before they succumb to disease 4,6,51 is consistent with the incapacity of infected DCs to regulate their CD40 and CD86 molecules, and the coincident failure of DCs to secrete IL-12 and other cytokines 20,23 . The naturally increased expression of B7-H1 in liver macrophages and parenchymal cells -thought to explain, at least in part, the poor immune responses to a wide range of antigens typically observed in the liver 44 -is particularly intriguing in view of the hepatotropic manifestation of filoviral disease (FIG. 1, BOX 1).…”

Section: Anergymentioning

confidence: 99%

How Ebola and Marburg viruses battle the immune system

2007

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PantropicTending towards the capacity to infect a wide range of cells and organs. CoagulopathyRefers to a group of conditions of the blood-clotting system in which bleeding is prolonged and excessive. Cell tropismA virus's affinity for or tendency towards preferential infection of certain cells. How Ebola and Marburg viruses battle the immune systemMansour Mohamadzadeh* ‡ , Lieping Chen ‡ , and Alan L. Schmaljohn* Abstract | The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. Filoviruses have provided thereby a new lens through which to examine the immune system itself. R E V I E W S Report Documentation PageForm Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.

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“…B7-H1/PD-1 engagement results in T cell apoptosis, altered T cell cytokine production, diminished proliferation, and reduced cytotoxicity of effector T cells (18 -20). CD8 ϩ T cells are more sensitive to the regulation of B7-H1 signals, as demonstrated by the delayed hepatic deletion of activated CD8 ϩ T cells and increased expansion and survival of CD8 ϩ T cells in B7-H1-deficient mice (21,22). Blocking B7-H1 signaling has been shown to improve antitumor immunity and immunotherapy (23,24).…”

Section: Targeting Molecular and Cellular Inhibitory Mechanisms For Imentioning

confidence: 99%

Targeting Molecular and Cellular Inhibitory Mechanisms for Improvement of Antitumor Memory Responses Reactivated by Tumor Cell Vaccine

Webster¹,

Thompson²,

Harris

et al. 2007

The Journal of Immunology

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Development of effective vaccination approaches to treat established tumors represents a focus of intensive research because such approaches offer the promise of enhancing immune system priming against tumor Ags via restimulation of pre-existing (memory) antitumoral helper and effector immune cells. However, inhibitory mechanisms, which function to limit the recall responses of tumor-specific immunity, remain poorly understood and interfere with therapies anticipated to induce protective immunity. The mouse renal cell carcinoma (RENCA) tumor model was used to investigate variables affecting vaccination outcomes. We demonstrate that although a whole cell irradiated tumor cell vaccine can trigger a functional antitumor memory response in the bone marrows of mice with established tumors, these responses do not culminate in the regression of established tumors. In addition, a CD103+ regulatory T (Treg) cell subset accumulates within the draining lymph nodes of tumor-bearing mice. We also show that B7-H1 (CD274, PD-L1), a negative costimulatory ligand, and CD4+ Treg cells collaborate to impair the recall responses of tumor-specific memory T cells. Specifically, mice bearing large established RENCA tumors were treated with tumor cell vaccination in combination with B7-H1 blockade and CD4+ T cell depletion (triple therapy treatment) and monitored for tumor growth and survival. Triple treatment therapy induced complete regression of large established RENCA tumors and raised long-lasting protective immunity. These results have implications for developing clinical antitumoral vaccination regimens in the setting in which tumors express elevated levels of B7-H1 in the presence of abundant Treg cells.

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B7-H1 Determines Accumulation and Deletion of Intrahepatic CD8+ T Lymphocytes

Cited by 350 publications

References 45 publications

PD-1:PD-L1 Interactions Contribute to the Functional Suppression of Virus-Specific CD8+ T Lymphocytes in the Liver

PD-1:PD-L1 Interactions Contribute to the Functional Suppression of Virus-Specific CD8+ T Lymphocytes in the Liver

How Ebola and Marburg viruses battle the immune system

Targeting Molecular and Cellular Inhibitory Mechanisms for Improvement of Antitumor Memory Responses Reactivated by Tumor Cell Vaccine

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