Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell Responses

Butte, Manish J.; Keir, Mary E.; Phamduy, Theresa B.; Sharpe, Arlene H.; Freeman, Gordon J.

doi:10.1016/j.immuni.2007.05.016

Cited by 1,519 publications

(1,317 citation statements)

References 55 publications

Supporting

Mentioning

1,270

Contrasting

Unclassified

Order By: Relevance

“…T-cell responses when characterized further exhibit phenotypic extracellular and intracellular markers typically associated with anergy. CTLA4 and PD1 cosignaling is involved in the induction of anergy [25][26][27] and these cell surface markers are enhanced on spleenocytes and CD4 + T cells during F. hepatica infection and following injection with FhTeg. Signaling through the CTLA4 receptor induces negative regulation of T-cell activation, which can lead to an unresponsive state in these cells [28].…”

Section: Discussionmentioning

confidence: 99%

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

Aldridge

O’Neill

2016

Eur J Immunol

View full text Add to dashboard Cite

FoxP3 + Treg cells and anergic T cells are the two regulatory phenotypes of T-cell responses associated with helminth infection. Here, we examine the T-cell responses in mice duringKeywords: Anergy r C-type lectin receptors r Dendritic cells r Helminth infection r Host-pathogen interactions r Mannose receptor r T-cell responses Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionHelminth parasites can survive within their hosts for many years by suppressing T-cell driven protective immune responses and Th1/Th2-mediated pathology through the induction of regulatory networks that suppress inflammatory responses [1][2][3][4]. These regulatory networks include regulatory T cells (Treg) that in the context of helminth infection is widely understood. Treg cells supCorrespondence: Dr. Sandra M. O'Neill e-mail: sandra.oneill@dcu.ie press the immune response to helminth-driven Th1/Th2 immune pathology through the induction of IL-10 and TGF-β. Brugia malayi, infection induces a regulatory response with enhanced FoxP3 expression and increased cell surface expression of CTLA4, a negative regulator of T-cell function [5] while Schistosoma haematobium infection in humans has also been associated with FoxP3 + Treg cells with the highest percentage of this cell population observed in younger patients [6]. However, less is currently known about the regulatory response termed in vivo anergy or adaptive tolerance.Few studies have examined the role of anergenic T cells during helminth infection. The induction of this cell population is thought C 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2016. 46: 1180-1192 Immunity to infection 1181 to be the result of the persistent contact of parasite antigen with immune cells during chronic helminth infection [7]. Anergenic T cells differ from Treg cells in that they do not express FoxP3 or produce IL-10 or TGF-β. Instead anergy is a hyporesponsive state with the failure of T cells to proliferate or produce cytokines when restimulated with antigens in vitro [8]. Anergic T cells do not secrete IL-2, a factor important for T-cell proliferation and effector responses. However, the addition of IL-2 can overcome this hyporesponsiveness, restoring helminth-driven T-cell responses. Gene analysis studies have identified a number of genes including Rnf128 (Grail), Itch, Egr2 and Egr3, and CblB that are involved in the induction and maintenance of T-cell anergy [9,10]. A number of helminth infections have shown T-cell anergy or Tcell hyporesponsiveness to be involved in immune suppression. Studies involving S. mansoni show the enhanced expression of GRAIL is linked to the suppression of Th2 cells and also using a filarial nematode, CD4 + T cells become functionally unresponsive [11,12]. Other studies indicate that anergenic-like T cells are the result of helminth infections, with an increase in anergenic markers and T-cell suppression [13][14][15][16]. Fasciola hepatica causes chronic liver d...

show abstract

Section: Discussionmentioning

confidence: 99%

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

Aldridge

O’Neill

2016

Eur J Immunol

View full text Add to dashboard Cite

show abstract

“…Thus, considering that the interaction between PD-1 and its ligand PD-L1 is involved in the inhibition of T cell responses, we hypothesized the participation of PD-1/PD-L1 in the process of T cell adaptation to persistent antigenic stimulation. Moreover, the possibility of a bidirectional inhibitory interaction between PD-L1 and CD80 expressed on T cells was recently described by Sharpe and coworkers (18) for the control of T cell responses. Therefore, we also analyzed the expression of CD80 and PD-L1 on naive and adapted T cells (Fig.…”

Section: Ag-adapted Cd4 ϩ T Cells Develop a Th1 Phenotype And Constitmentioning

confidence: 95%

Reviving Function in CD4+ T Cells Adapted to Persistent Systemic Antigen

Rivas

Weatherly

Hazzan

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

In bone marrow-transplanted patients, chronic graft-versus-host disease is a complication that results from the persistent stimulation of recipient minor histocompatibility Ag (mHA)-specific T cells contained within the graft. In this study, we developed a mouse model where persistent stimulation of donor T cells by recipient’s mHA led to multiorgan T cell infiltration. Exposure to systemic mHA, however, deeply modified T cell function and chronically stimulated T cells developed a long-lasting state of unresponsiveness, or immune adaptation, characterized by their inability to mediate organ immune damages in vivo. However, analysis of the gene expression profile of adapted CD4+ T cells revealed the specific coexpression of genes known to promote differentiation and function of Th1 effector cells as well as genes coding for proteins that control T cell activity, such as cell surface-negative costimulatory molecules and regulatory cytokines. Strikingly, blockade of negative costimulation abolished T cell adaptation and stimulated strong IFN-γ production and severe multiorgan wasting disease. Negative costimulation was also shown to control lethal LPS-induced toxic shock in mice with adapted T cells, as well as the capacity of adapted T cells to reject skin graft. Our results demonstrate that negative costimulation is the molecular mechanism used by CD4+ T cells to adapt their activity in response to persistent antigenic stimulation. The effector function of CD4+ T cells that have adapted to chronic Ag presentation can be activated by stimuli strong enough to overcome regulatory signals delivered to the T cells by negative costimulation.

show abstract

“…This exhausted phenotype is mediated by programmed cell death protein (PD‐1) (Fig. 1c), and results in CD8 + T cells with impaired proliferation and cytokine secretion 31, 134, 135. As recent findings have identified pertinent roles of CD8 + T cells in the clearance of erythrocytic stage parasites via different effector functions, including cytokine secretion (particularly IFN‐ γ ),136, 137, 138 their loss may be associated with reduced inflammatory responses at the cost of effective parasite clearance, which might explain higher parasitaemias at high exposure levels.…”

Section: Mechanisms Of Reduced Inflammation At High Exposure Levelsmentioning

confidence: 99%

Evaluating antidisease immunity to malaria and implications for vaccine design

Ademolue

Awandare

2017

Immunology

View full text Add to dashboard Cite

SummaryImmunity to malaria could be categorized broadly as antiparasite or antidisease immunity. While most vaccine research efforts have focused on antiparasite immunity, the evidence from endemic populations suggest that antidisease immunity is an important component of natural immunity to malaria. The processes that mediate antidisease immunity have, however, attracted little to no attention, and most interests have been directed towards the antibody responses. This review evaluates the evidence for antidisease immunity in endemic areas and discusses the possible mechanisms responsible for it. Given the key role that inflammation plays in the pathogenesis of malaria, regulation of the inflammatory response appears to be a major mechanism for antidisease immunity in naturally exposed individuals.

show abstract

Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell Responses

Cited by 1,519 publications

References 55 publications

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

Reviving Function in CD4+ T Cells Adapted to Persistent Systemic Antigen

Evaluating antidisease immunity to malaria and implications for vaccine design

Contact Info

Product

Resources

About