Bystander T cell activation – implications for HIV infection and other diseases

Bangs, Sarah C.; McMichael, Andrew J.; Xu, Xiao-Ning

doi:10.1016/j.it.2006.09.006

Cited by 59 publications

(48 citation statements)

References 67 publications

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“…HIV-1 infection is characterized by sustained high levels of "general" immune activation (32)(33)(34)(35), which is reflected by increased expression of activation markers on T lymphocytes (1), increased cell cycling, and increased propensity of apoptosis (7,(36)(37)(38). The mechanisms underlying hyperactivation of non-HIV-1 specific T cells during chronic HIV-1 infection are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…hence expanded T lymphocytes exhibit a bias toward certain specificities (including persistent herpes or nonpersistent viral Ags), and 2) whether there is a contribution of inflammatory mediators (e.g., proinflammatory cytokines and TLR agonists) leading to CD4 + or CD8 + T cell activation independent of TCR triggering, which is referred to as "bystander activation" (7,9).…”

Section: Discussionmentioning

confidence: 99%

“…Usually only 6-8% of all circulating CD8 + T cells are HIV-1 specific (4,5), whereas the level of CD8 + T cells exhibiting activated phenotypes (CD38 + HLA-DR + ) can be as high as 60% (6). The mechanisms underlying this increased activation of non-HIV-1-specific T cells are still poorly defined (7,8).…”

Section: Ontinuous Loss Of Cd4 + T Cells and Hyperactivation Of T Cmentioning

confidence: 99%

“…It is believed that most of these cells are activated by nonspecific mechanisms, including cross-reactivity and cytokine-driven activation (7,9), a phenomenon referred to as "bystander activation." Furthermore, systemic translocation of gut microbial products including LPS, owing to increased permeability of the gut epithelium, is suggested to contribute to general immune activation (10).…”

Section: Ontinuous Loss Of Cd4 + T Cells and Hyperactivation Of T Cmentioning

confidence: 99%

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CD8+ T Cells Are Activated in an Antigen-Independent Manner in HIV-Infected Individuals

Bastidas

Graw

Smith

et al. 2014

The Journal of Immunology

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Hyperactivation of T cells, particularly of CD8+ T cells, is a hallmark of chronic HIV 1 (HIV-1) infection. Little is known about the antigenic specificities and the mechanisms by which HIV-1 causes activation of CD8+ T cells during chronic infection. We report that CD8+ T cells were activated during in vivo HIV-1 replication irrespective of their Ag specificity. Cytokines present during untreated HIV-1 infection, most prominently IL-15, triggered proliferation and expression of activation markers in CD8+ T cells, but not CD4+ T cells, in the absence of TCR stimulation. Moreover, LPS or HIV-1–activated dendritic cells (DCs) stimulated CD8+ T cells in an IL-15–dependent but Ag-independent manner, and IL-15 expression was highly increased in DCs isolated from viremic HIV-1 patients, suggesting that CD8+ T cells are activated by inflammatory cytokines in untreated HIV-1 patients independent of Ag specificity. This finding contrasts with CD4+ T cells whose in vivo activation seems biased toward specificities for persistent Ags. These observations explain the higher abundance of activated CD8+ T cells compared with CD4+ T cells in untreated HIV-1 infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Ontinuous Loss Of Cd4 + T Cells and Hyperactivation Of T Cmentioning

confidence: 99%

Section: Ontinuous Loss Of Cd4 + T Cells and Hyperactivation Of T Cmentioning

confidence: 99%

See 2 more Smart Citations

CD8+ T Cells Are Activated in an Antigen-Independent Manner in HIV-Infected Individuals

Bastidas

Graw

Smith

et al. 2014

The Journal of Immunology

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“…Under certain circumstances, T cells can be activated through bystander mechanisms that do not involve specific Ag signaling through the TCR (12). Ag-independent activation of both naive and memory resting T cells can be elicited in vitro using a combination of IL-2, TNF-␣, and IL-6 (13).…”

mentioning

confidence: 99%

TGF-β1 Regulates Antigen-Specific CD4+ T Cell Responses in the Periphery

Robinson

Gorham

2007

The Journal of Immunology

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T cell expansion typically is due to cognate interactions with specific Ag, although T cells can be experimentally activated through bystander mechanisms not involving specific Ag. TGF-β1 knockout mice exhibit a striking expansion of CD4+ T cells in the liver by 11 days of age, accompanied by CD4+ T cell-dependent necroinflammatory liver disease. To examine whether hepatic CD4+ T cell expansion in TGF-β1−/− mice is due to cognate TCR-peptide interactions, we used spectratype analysis to examine the diversity in TCR Vβ repertoires in peripheral CD4+ T cells. We reasoned that Ag-nonspecific T cell responses would yield spectratype profiles similar to those derived from control polyclonal T cell populations, whereas Ag-specific T cell responses would yield perturbed spectratype profiles. Spleen and liver CD4+ T cells from 11-day-old TGF-β1−/− mice characteristically exhibited highly perturbed nonpolyclonal distributions of TCR Vβ CDR3 lengths, indicative of Ag-driven T cell responses. We quantitatively assessed spectratype perturbation to derive a spectratype complexity score. Spectratype complexity scores were considerably higher for TGF-β1−/− CD4+ T cells than for TGF-β1+/− CD4+ T cells. TCR repertoire perturbations were apparent as early as postnatal day 3 and preceded both hepatic T cell expansion and liver damage. By contrast, TGF-β1−/− CD4+ single-positive thymocytes from 11-day-old mice exhibited normal unbiased spectratype profiles. These results indicate that CD4+ T cells in TGF-β1−/− mice are activated by and respond to self-Ags present in the periphery, and define a key role for TGF-β1 in the peripheral regulation of Ag-specific CD4+ T cell responses.

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Mycobacterium tuberculosisPstS1 amplifies IFN‐γ and induces IL‐17/IL‐22 responses by unrelated memory CD4⁺T cells via dendritic cell activation

et al. 2013

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Bystander T cell activation – implications for HIV infection and other diseases

Cited by 59 publications

References 67 publications

CD8+ T Cells Are Activated in an Antigen-Independent Manner in HIV-Infected Individuals

CD8+ T Cells Are Activated in an Antigen-Independent Manner in HIV-Infected Individuals

TGF-β1 Regulates Antigen-Specific CD4+ T Cell Responses in the Periphery

Mycobacterium tuberculosisPstS1 amplifies IFN‐γ and induces IL‐17/IL‐22 responses by unrelated memory CD4⁺T cells via dendritic cell activation

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Bystander T cell activation – implications for HIV infection and other diseases

Cited by 59 publications

References 67 publications

CD8+ T Cells Are Activated in an Antigen-Independent Manner in HIV-Infected Individuals

CD8+ T Cells Are Activated in an Antigen-Independent Manner in HIV-Infected Individuals

TGF-β1 Regulates Antigen-Specific CD4+ T Cell Responses in the Periphery

Mycobacterium tuberculosisPstS1 amplifies IFN‐γ and induces IL‐17/IL‐22 responses by unrelated memory CD4+T cells via dendritic cell activation

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Product

Resources

About

Mycobacterium tuberculosisPstS1 amplifies IFN‐γ and induces IL‐17/IL‐22 responses by unrelated memory CD4⁺T cells via dendritic cell activation