Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

Thompson, Bruce S.; Mata-Haro, Verónica; Casella, Carolyn R.; Mitchell, Thomas C.

doi:10.1002/eji.200526132

Cited by 10 publications

(10 citation statements)

References 38 publications

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“…Also, the death of T cells throughout the Ag-driven clonal expansion in vivo is proportional to the Ag concentration (71) and is counteracted by the presence of TLR ligands through an unknown mechanism independent of Bim, Bcl-2, and Bcl-x L (72). As TLR stimulation leads to a potent proinflammatory response and melatonin level is increased during inflammation, it is reasonable to conceive that melatonin-mediated downregulation of CD95L may play a role in the survival of T cells during an immune response.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation

Pedrosa

Weinlich

Mognol

et al. 2010

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation

Pedrosa

Weinlich

Mognol

et al. 2010

The Journal of Immunology

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“…These results are in agreement with the report showing that in the absence of TLR ligands, activated T cells divide well but accumulate poorly, largely due to a higher death rate. 27 There are two possible signaling pathways triggered by the LPS receptor TLR4. One is dependent on MyD88 and the other uses TRIF as the adaptor molecule.…”

Section: Discussionmentioning

confidence: 99%

TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

et al. 2008

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Antigen-presenting cells (APCs) control T-cell responses by multiple mechanisms, including the expression of co-stimulatory molecules and the production of cytokines and other mediators that control T-cell proliferation, survival and differentiation. Here, we demonstrate that soluble factor(s) produced by Toll-like receptor (TLR)-activated APCs suppress activation-induced cell death (AICD). This effect was observed in non-stimulated APCs, but it was significantly increased after lipopolysaccharide (LPS) treatment. Using different KO mice, we found that the LPS-induced protective factor is dependent on TLR4/MyD88. We identified the protective factor as prostaglandin E 2 (PGE 2 ) and showed that both APC-derived supernatants and PGE 2 prevented CD95L upregulation in T cells in response to TCR/CD3 stimulation, thereby avoiding both AICD and activated T cell killing of target macrophages. The PGE 2 receptors, EP2 and EP4, appear to be involved since pharmacological stimulation of these receptors mimics the protective effect on T cells and their respective antagonists interfere with the protection induced by either APCs derived or synthetic PGE 2 . Finally, the engagement of EP2 and EP4 synergistically activates protein kinase A (PKA) and exchange protein directly activated by cAMP pathways to prevent AICD. Taken together, these results indicate that APCs can regulate T-cell levels of CD95L by releasing PGE 2 in response to LPS through a TLR4/MyD88-dependent pathway, with consequences for both T cell and their own survival. Cell Death and Differentiation (2008) 15, 1901-1909 doi:10.1038/cdd.2008 ; published online 26 September 2008Proper activation of T cells is imperative to achieve an efficient immunity against pathogens and tumors and, at the same time, to avoid undesirable collateral effects, such as the appearance of autoimmune diseases. Secondary lymphoid organs provide a particular microenvironment specialized in assembling all the cohorts necessary to perform such a remarkable task. 1 In the presence of antigens, antigenpresenting cells (APCs) and their soluble products, including a variety of cytokines, lipid mediators and chemokines, T cells are activated through the engagement of their T-cell receptors (TCR) and co-stimulatory molecules. As a result, T cells can proliferate, differentiate to effector or memory cells, or eventually die.Deletion of autoreactive T cells is one of the key mechanisms involved in the process of peripheral tolerance that helps to prevent the appearance of autoimmune diseases. 2 Similarly, elimination of chronically stimulated T cells that can potentially be harmful to the host by the means of the production of abnormal levels of inflammatory cytokines is another feature of an efficient immune system. Finally, death of effector T cells at the end of an immune response is a very important homeostatic mechanism designed to shrink an enlarged, no longer necessary cell population that can compete for growth and survival factors with newly activated antigen-specific T-cell clones. In a...

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“…LPS is a natural adjuvant that increases the number of cell divisions and the rate of cell survival during and after T cell activation and clonal expansion (1,39,40). SmMPLA also acts effectively as an adjuvant for initial T cell clonal expansion in vivo, which we and others have shown is dependent on the TLR4 signaling adaptor TRIF (25,26). Using a standard adoptive-transfer model of ovalbumin-specific T cell receptor (TCR) transgenic (Tg) CD8 and CD4 T cells (OTI.SJL and OTII.SJL cells, respectively), we assessed the effects of LT-LPS on initial T cell clonal expansion compared to the effects elicited with SmLPS and SmMPLA.…”

Section: Naturally Occurring Lt-lps Preparations Promote a Balanced Imentioning

confidence: 77%

“…The doses of antigen and adjuvants used in each protocol were chosen to optimize the adjuvant effects. Previous studies had also determined that 2-to 3-fold more SmMPLA than SmLPS is needed to elicit similar levels of peak T cell clonal expansion in different groups of mice (26), and the LT-LPS amounts used were matched to that of SmMPLA. Because stock LT-LPS preparations were suspended in DMSO, enough DMSO was added to each vaccine preparation to control for the DMSO present in the LT-LPS-adjuvanted vaccine preparations.…”

Section: Naturally Occurring Lt-lps Preparations Promote a Balanced Imentioning

confidence: 99%

“…Interestingly, the specific set of genes activated after partial or weak TLR4/MD2 agonism with P. gingivalis LPS in vitro was focused on cellular immune responses, with the majority of the genes associated with either immune cell adhesion or cell trafficking (18). Similarly, MPLA-stimulated cells have demonstrated a bias toward utilizing the TLR4 signaling adaptor protein TRIF, as opposed to MyD88, in eliciting cellular responses (25), which could help explain the retention of immune-stimulatory activities even when toxic activities are markedly decreased (26)(27)(28).…”

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confidence: 99%

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Adjuvant Activity of Naturally Occurring Monophosphoryl Lipopolysaccharide Preparations from Mucosa-Associated Bacteria

Chilton

Hadel

et al. 2013

Infect Immun

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c Natural heterogeneity in the structure of the lipid A portion of lipopolysaccharide (LPS) produces differential effects on the innate immune response. Gram-negative bacterial species produce LPS structures that differ from the classic endotoxic LPS structures. These differences include hypoacylation and hypophosphorylation of the diglucosamine backbone, both differences known to decrease LPS toxicity. The effect of decreased toxicity on the adjuvant properties of many of these LPS structures has not been fully explored. Here we demonstrate that two naturally produced forms of monophosphorylated LPS, from the mucosa-associated bacteria Bacteroides thetaiotaomicron and Prevotella intermedia, function as immunological adjuvants for antigen-specific immune responses. Each form of mucosal LPS increased vaccination-initiated antigen-specific antibody titers in both quantity and quality when given simultaneously with vaccine antigen preparations. Interestingly, adjuvant effects on initial T cell clonal expansion were selective for CD4 T cells. No significant increase in CD8 T cell expansion was detected. MyD88/Tolllike receptor 4 (TLR4) and TRIF/TLR4 signaling pathways showed equally decreased signaling with the LPS forms studied here as with endotoxic LPS or detoxified monophosphorylated lipid A (MPLA). Natural monophosphorylated LPS from mucosa-associated bacteria functions as a weak but effective adjuvant for specific immune responses, with preferential effects on antibody and CD4 T cell responses over CD8 T cell responses.

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Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

Cited by 10 publications

References 38 publications

Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation

Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation

TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

Adjuvant Activity of Naturally Occurring Monophosphoryl Lipopolysaccharide Preparations from Mucosa-Associated Bacteria

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