Bystander T Cells: A Balancing Act of Friends and Foes

Whiteside, Sarah; Snook, Jeremy P.; Williams, Matthew A.; Weis, Janis J.

doi:10.1016/j.it.2018.10.003

Cited by 88 publications

(85 citation statements)

References 148 publications

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“…4,12,15,21,[51][52][53][54][55][56][57] Nevertheless, based on currently available evidence, it is safe to assume that although ICDelicited antigen-specific T cell clones might be "rich" in terms of TCR diversity (i.e. overall amount of T cells with unique antigen-reactive TCRs), [58][59][60][61][62][63] their "evenness" (i.e. uniform distribution of unique TCR-possessing T cells) might be limited due to various constrains specific to oncological contexts.…”

Section: Introductionmentioning

confidence: 99%

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

et al. 2020

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The term 'immunogenic cell death' (ICD) denotes an immunologically unique type of regulated cell death that enables, rather than suppresses, T cell-driven immune responses that are specific for antigens derived from the dying cells. The ability of ICD to elicit adaptive immunity heavily relies on the immunogenicity of dying cells, implying that such cells must encode and present antigens not covered by central tolerance (antigenicity), and deliver immunostimulatory molecules such as damage-associated molecular patterns and cytokines (adjuvanticity). Moreover, the host immune system must be equipped to detect the antigenicity and adjuvanticity of dying cells. As cancer (but not normal) cells express several antigens not covered by central tolerance, they can be driven into ICD by some therapeutic agents, including (but not limited to) chemotherapeutics of the anthracycline family, oxaliplatin and bortezomib, as well as radiation therapy. In this Trial Watch, we describe current trends in the preclinical and clinical development of ICD-eliciting chemotherapy as partner for immunotherapy, with a focus on trials assessing efficacy in the context of immunomonitoring.

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Section: Introductionmentioning

confidence: 99%

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

et al. 2020

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“…There is also evidence that infection with the parasite Plasmodium falciparum can induce some MAIT cell activation in humans, presumably in the absence of TCR agonist signals (9). This inflammation-driven, TCR-independent mechanism of activation is akin to the phenomenon of bystander-activation in conventional memory T cells (10,11). The physiological significance and the consequences of inflammation-driven activation of MAIT cells are still largely unclear.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokines Induce Sustained CTLA-4 Cell Surface Expression on Human MAIT Cells

Berkson

Slichter

DeBerg³

et al. 2020

ImmunoHorizons

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Mucosal-associated invariant T (MAIT) cells acquire effector function in response to proinflammatory signals, which synergize with TCR-mediated signals. We asked if cell-intrinsic regulatory mechanisms exist to curtail MAIT cell effector function akin to the activation-induced expression of inhibitory receptors by conventional T cells. We examined human MAIT cells from blood and oral mucosal tissues by RNA sequencing and found differential expression of immunoregulatory genes, including CTLA-4, by MAIT cells isolated from tissue. Using an ex vivo experimental setup, we demonstrate that inflammatory cytokines were sufficient to induce CTLA-4 expression on the MAIT cell surface in the absence of TCR signals. Even brief exposure to the cytokines IL-12, IL-15, and IL-18 was sufficient for sustained CTLA-4 expression by MAIT cells. These data suggest that control of CTLA-4 expression is fundamentally different between MAIT cells and conventional T cells. We propose that this mechanism serves to limit MAIT cell-mediated tissue damage. ImmunoHorizons, 2020, 4: 14-22.

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“…Vascular endothelial cells express major histocompatibility class II molecules (MHCII) and can activate naive or preciously activated CD4 + T‐cells via conventional antigen presentation to the T‐cell receptor (TCR) bearing T‐cells 46 . In an inflammatory environment, during autoimmunity, cancer, and bacterial or viral infection T‐cells have been shown to be activated also independently of antigen presentation to the TCR 47 . To investigate if the activation of MOLT‐4 T‐lymphoblasts by C3a/C5a simulated HUVECs is MHCII dependent, we performed neutralization experiments with anti‐MHCII‐β‐chain‐specific antibody.…”

Section: Resultsmentioning

confidence: 99%

“…The nonconventional activation of T‐cell appears to occur primarily in a highly inflamed microenvironment, including that during infection, autoimmunity, and cancer. Although the mechanism(s) that drive the nonconventional activation of T‐cells is poorly understood it has been proposed to occur through the T‐cells interacting with other receptors and costimulatory molecules that in an inflamed microenvironment are upregulated and highly expressed and greatly lower the threshold for the activation naïve T‐cells 47 . In an inflamed environment a high level of the complement anaphylatoxin peptides would be present in the circulation surrounding vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

In response to complement anaphylatoxin peptides C3a and C5a, human vascular endothelial cells migrate and mediate the activation of B‐cells and polarization of T‐cells

Shivshankar

Mueller‐Ortiz

et al. 2020

FASEB j.

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The vascular endothelium has been discovered in the past several years to be important in shaping the cellular immune response. During the immune response the vascular endothelium is constantly perturbed by biologically potent molecules, including the complement activation peptides, C3a and C5a. Despite the importance of C3a and C5a in inflammation and immunity, their role in modulating lymphocyte function via activation of vascular endothelial cells is unknown. Accordingly, we investigated the regulated expression of the C3a and C5a receptors (complement anaphylatoxin C3a receptor [C3aR] and complement anaphylatoxin C5a receptor 1 [C5aR1]) on human umbilical vascular endothelial cells (HUVECs) and examined how C3a or C5a activation of HUVECs affects the activation and polarization of lymphatic cells. Our findings demonstrated that C3a and C5a increase C3aR and C5aR1 expression by HUVECs as well as directing their cellular transmigration and spreading through transwell filters. Moreover, C3a‐ or C5a‐stimulated endothelial cells: (1) caused activation of B‐lymphoblasts with significant increase in Fas Ligand (CD95L) (FasL), CD69, and IL‐R1 expression, and (2) skewed T‐lymphoblast cells toward a Th1 subtype, (CD4+/CCR5+) that correlated with significant increase of IFN‐γ. Collectively, these data indicate that C3a and C5a signaling is important in the activation and polarization of lymphocytes as they traffic through the vascular endothelium during the immune response.

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Bystander T Cells: A Balancing Act of Friends and Foes

Cited by 88 publications

References 148 publications

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

Inflammatory Cytokines Induce Sustained CTLA-4 Cell Surface Expression on Human MAIT Cells

In response to complement anaphylatoxin peptides C3a and C5a, human vascular endothelial cells migrate and mediate the activation of B‐cells and polarization of T‐cells

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