T Cell Stimulation In Vivo by Lipopolysaccharide (LPS)

Tough, David F.; Sun, Siquan; Sprent, Jonathan

doi:10.1084/jem.185.12.2089

Cited by 305 publications

(249 citation statements)

References 27 publications

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“…Conversely, expansions of anti-viral and antibacterial responses were also noted following vaccination with TT [10,11]. Furthermore, infusion of LPS, which mimics bacterial infections, induces indirect activation of T cells in healthy volunteers [12], confirming similar results observed in mouse models [13,14]. In vitro, human CD4 1 memory T cells appear to be preferential targets for bystander activation, generating a distinct gene expression profile and elevating levels of the extrinsic pathway of apoptosis [15].…”

Section: Introductionmentioning

confidence: 65%

Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

et al. 2010

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Antigen-specific CD4 1 T cells are central to natural and vaccine-induced immunity. An ongoing antigen-specific T-cell response can, however, influence surrounding T cells with unrelated antigen specificities. We previously observed this bystander effect in healthy human subjects following recall vaccination with tetanus toxoid (TT). Since this interplay could be important for maintenance of memory, we have moved to a mouse model for further analysis. We investigated whether boosting memory CD4 1 T cells against TT in vivo would influence injected CD4 1 TCR transgenic T cells (OT-II) specific for an unrelated OVA peptide. If OT-II cells were pre-activated with OVA peptide in vitro, these cells showed a bystander proliferative response during the ongoing parallel TT-specific response. Bystander proliferation was dependent on boosting of the TT-specific memory response in the recipients, with no effect in naive mice. Bystander stimulation was also proportional to the strength of the TT-specific memory T-cell response. T cells activated in vitro displayed functional receptors for IL-2 and IL-7, suggesting these as potential mediators. This crosstalk between a stimulated CD4 1 memory T-cell response and CD4 1 T cells activated by an unrelated antigen could be important in human subjects continually buffeted by environmental antigens.

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Section: Introductionmentioning

confidence: 65%

Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

et al. 2010

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“…This increase is driven largely by the expansion of CD8 + CD44 high memory Tcells. Exogenous administration of IL-15 or induction of host expression of IL-15 in wildtype mice by reagents, such as poly I:C, lipopolysaccharide (LPS) and type I-IFNs, causes a selective increase in the proliferation of CD8 + CD44 high T cells in vivo [29][30][31]. Exogenous administration of IL-7 to mice enhances T-cell number and function [32,33] and, in both intact and immunodeficient non-human primates, causes a considerable yet reversible increase in the circulating levels of naïve and Ag-experienced CD4 + and CD8 + T cells [34].…”

Section: Evidence For the Presence Of Homeostatic Cellular Cytokine 'mentioning

confidence: 99%

“…Damage inflicted on the intestinal tract might permit the translocation of bacterial products, such as LPS, into the systemic circulation [79]. LPS activates T cells in vivo [31] and might enhance the antitumor response. Thus, proinflammatory cytokines and microbial products provide crucial 'danger signals' for the activation and maturation of DCs, thus enhancing T cell-mediated tumor treatment.…”

Section: Effects Of Lymphodepleting Radiation and Chemotherapy On Apcmentioning

confidence: 99%

“…Modulation of adoptively transferred cells either through overproduction of cytokines, such as IL-7, IL-15 [43] or IL-21, or cytokine receptors, such as IL-7Rα and IL-15Rα, are currently being explored as possible means to enhance T-cell function in vivo. Reagents that stimulate host expression of IL-15 and IL-15Rα [30,31,82], including type I IFNs, CpG DNA, LPS, dsRNA and dsRNAimitators, such as polyI:C, might enhance the functionality of adoptively transferred cells.…”

Section: Therapeutic Implications and Future Directionsmentioning

confidence: 99%

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Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Klebanoff

Khong

Antony

et al. 2005

Trends in Immunology

404

288

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Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine 'sinks' for homeostatic γ C -cytokines, such as interleukin-7 (IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4 + CD25 + regulatory T (Treg) cells that suppress tumorreactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigenpresenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer.

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“…It is known that LPS is a powerful adjuvant for CD8 1 T-cell activation [17,18]. However, whether LPS directly or indirectly activates CD8 1 T cells is unclear.…”

mentioning

confidence: 99%

Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex

Komai-Koma¹,

Gilchrist²,

Xu³

2009

Eur J Immunol

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LPS comprises a major PAMP and is a key target of the immune system during bacterial infection. While LPS can be recognised by innate immune cells via the TLR4 complex, it is unknown whether T lymphocytes, especially CD8 1 T cells are also capable of doing so. We report here that naïve human CD8 1 T cells, after activation by TCR stimulation, express surface TLR4 and CD14. These activated CD8 1 T cells can then secrete high concentrations of IFN-c, granzyme and perforin in response to LPS. These effects can be specifically inhibited using siRNA for TLR4. Furthermore, LPS can synergise with IL-12 to polarise the CD8 1 T cells into cytotoxic T-cell 1 (Tc1) that produce IFN-c but not IL-4, with or without TCR activation. Moreover, CD8 1 CD45RO 1 memory T cells constitutively expressed TLR4 and markedly enhanced IFN-c production when stimulated with LPS. In contrast, activated murine CD8 1 T cells lack TLR4 and CD14 expression and fail to respond to LPS for proliferation and cytokine production. Thus, human but not murine CD8 1 T cells are able to directly recognise bacterial LPS via LPS receptor complex and TLR4 provides a novel signal for the activation of effector and memory human CD8 1 T cells.Key words: CD14 . CD8 1 T cells . Tc1 . LPS . TLR Supporting Information available online IntroductionLPS is an abundant glycolipid in the outer-membrane of Gramnegative bacteria [1][2][3]. It consists of hydrophobic lipid A, the o-polysaccharide chain and a core oligosaccharide [3][4][5]. LPS is perhaps the most well-studied microbial molecule due to its powerful immune activating properties, extremely stable nature and wide distribution in the environment [1][2][3]. It is the key molecule responsible for the bacteria-triggered inflammatory response resulting in organ failure and death [1][2][3]. LPS is also closely associated with pathogenesis of many inflammatory diseases [1][2][3][4]. Despite this, the proinflammatory effects of LPS when harnessed may be beneficial; its powerful effect on both innate and adaptive immunity may provide a new generation of immune adjuvants for vaccine development against infection and cancer [2-4]. Therefore, a clearer understanding of how host recognises LPS is fundamentally important.TLR are a group of evolutionarily developed pathogen-pattern recognition receptors that are widely distributed on immune cells [3,5]. At least ten members of the TLR family in humans have been identified. These recognise different microbial products from bacteria, virus, fungi and parasites [2][3][4]. Host cells recognise LPS via a receptor complex consisting of TLR4, CD14 and MD2 in which LPS only signals through TLR4 and triggers cellular activation and expression of inflammatory genes [2][3][4]. Since TLR was originally identified in Drosophila, which lacks an adaptive immune system, the initial belief was that recognition of pathogen products was a characteristic of innate cells bearing 1564TLR [5,6]. However, the role of T cells bearing TLR in pathogen recognition is less well understood.Growing evide...

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T Cell Stimulation In Vivo by Lipopolysaccharide (LPS)

Cited by 305 publications

References 27 publications

Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex

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T Cell Stimulation In Vivo by Lipopolysaccharide (LPS)

Cited by 305 publications

References 27 publications

Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex

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Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Direct recognition of LPS by human but not murine CD8⁺ T cells via TLR4 complex