Stress-activated Dendritic Cells (DC) Induce Dual Interleukin (IL)-15- and IL1β-mediated Pathways, Which May Elicit CD4+ Memory T Cells and Interferon (IFN)-stimulated Genes

Wang, Yufei; Lavender, Paul; Watson, Julie; Arno, Matthew; Lehner, Thomas

doi:10.1074/jbc.m115.645754

Cited by 10 publications

(18 citation statements)

References 62 publications

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“…7 F ). The data are consistent with the present and previous finding ( 15 ) of optimum memory T cell expression requiring both H (DC-mediated maIL-15) and I (DC-mediated IL-1β) pathways, whereas memory B cells require only the H pathway.…”

Section: Resultssupporting

confidence: 93%

“…We have previously demonstrated that maIL-15 and IL-1β are up-regulated in CD11C + splenic DC when BALB/c mice were treated with stress agents and OVA ( 10 ). We hypothesized from our studies with CD4 + T cells ( 15 ) that the homeostatic pathway is driven by interaction between maIL-15DC and IL-15Ra on B cells, whereas the inflammasome pathway is driven by interaction between IL-1 expressed by DC and IL-1R on B cells. Analysis of variance of maIL-15 in splenic CD11C + DC showed significant difference between the stress agent-treated mice without OVA immunization ( F = 3.868, p = 0.021), although separately only alum reached significance ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The homeostatic (H) pathway activates NFκB, which transactivates maIL-15 expression on DC, binding IL-15R on CD4 + T cells and inducing CD40L expression ( 9 ). Recently, we have presented evidence in vitro in primary human T cells that both the homeostatic (H) and inflammasome (I) pathways are required for optimal CD4 + CD45RO + memory T cell expression ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Cellular Stress on T and B Cell Memory Pathways in Immunized and Unimmunized BALB/c Mice

Wang

Rahman

Mistry

et al. 2016

Journal of Biological Chemistry

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Immunological memory is a fundamental function of vaccination. The antigenic breakdown products of the vaccine may not persist, and undefined tonic stimulation has been proposed to maintain the specific memory. We have suggested that cellular stress agents to which the immune cells are constantly exposed may be responsible for tonic stimulation. Here we have studied four stress agents: sodium arsenite, an oxidative agent; Gramicidin, eliciting K+ efflux and calcium influx; dithiocarbamate, a metal ionophore; and aluminum hydroxide (alum), an immunological adjuvant. The aims of this study are to extend these investigations to T and B cell responses of unimmunized and ovalbumin (OVA)-immunized BALB/c mice, and furthermore, to ascertain whether stress is involved in optimal expression of memory B cells, as demonstrated in CD4+ T cells. Examination of the homeostatic pathway defined by IL-15/IL-15R (IL-15 receptor) interaction and the inflammasome pathway defined by the IL-1-IL-1R interaction between dendritic cells (DC) and CD4+ T cells suggests that both pathways are involved in the development of optimal expression of CD4+CD45RO+ memory T cells in unimmunized and OVA-immunized BALB/c mice. Furthermore, significant direct correlation was found between CD4+CD44+ memory T cells and both IL-15 of the homeostatic and IL-1β of the inflammasome pathways. However, CD19+CD27+ memory B cells in vivo seem to utilize only the IL-15/IL-15R homeostatic pathway, although the proliferative responses are enhanced by the stress agents. Altogether, stress agents may up-regulate unimmunized and OVA-immunized CD4+CD44+ memory T cells by the homeostatic and inflammasome pathways. However, the CD19+CD27+ memory B cells utilize only the homeostatic pathway.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Effect of Cellular Stress on T and B Cell Memory Pathways in Immunized and Unimmunized BALB/c Mice

Wang

Rahman

Mistry

et al. 2016

Journal of Biological Chemistry

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“…Supporting this notion, recent data showed that antigen-independent immunological memory could be maintained in CD4 + T cells by repetitive stressors of various kinds (Wang et al, 2015). Therefore, it is possible that T cells can be “educated” in the context of antigen-free chronic stress to exert effects on target organs, including the brain.…”

Section: Adaptive Immunity In Affective Disordersmentioning

confidence: 90%

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

Herkenham

Kigar

2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Clinical and basic studies of functional interactions between adaptive immunity, affective states, and brain function are reviewed, and the neural, humoral, and cellular routes of bidirectional communication between the brain and the adaptive immune system are evaluated. In clinical studies of depressed populations, lymphocytes—the principal cells of the adaptive immune system—exhibit altered T cell subtype ratios and CD4+ helper T cell polarization profiles. In basic studies using psychological stress to model depression, T cell profiles are altered as well, consistent with stress effects conveyed by the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Lymphocytes in turn have effects on behavior and CNS structure and function. CD4+ T cells in particular appear to modify affective behavior and rates of hippocampal dentate gyrus neurogenesis. These observations force the question of how such actions are carried out. CNS effects may occur via cellular and molecular mechanisms whereby effector memory T cells and the cytokine profiles they produce in the blood interact with the blood-brain barrier in ways that remain to be clarified. Understanding the mechanisms by which T cells polarize and interact with the brain to alter mood states is key to advances in the field, and may permit development of therapies that target cells in the periphery, thus bypassing problems associated with bioavailability of drugs within the brain.

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“…These 2 pathways initiate acquired immune responses, including expansion of T-cell clones and differentiation into effector cells. A third signaling pathway is delivered to T-cells by DCs [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Culture and Identification of Mouse Bone Marrow-Derived Dendritic Cells and Their Capability to Induce T Lymphocyte Proliferation

Wang

et al. 2016

Med Sci Monit

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BackgroundThe aim of this study was to establish a culture method for mouse dendritic cells (DCs) in vitro and observe their morphology at different growth stages and their ability to induce the proliferation of T lymphocytes.Material/MethodsGranulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used in combination to induce differentiation of mouse bone marrow (BM) mononucleocytes into DCs. The derived DCs were then assessed for morphology, phenotype, and function.ResultsThe mouse BM-derived mononucleocytes had altered cell morphology 3 days after induction by GM-CSF and IL-4 and grew into colonies. Typical dendrites appeared 8 days after induction. Many mature DCs were generated, with typical dendritic morphology observed under scanning electron microscopy. Expression levels of CD11c, a specific marker of BM-derived DCs, and of co-stimulatory molecules such as CD40, CD80, CD86, and MHC-II were elevated in the mature DCs. Furthermore, the mature DCs displayed a strong potency in stimulating the proliferation of syngenic or allogenic T lymphocytes.ConclusionsMouse BM-derived mononucleocytes cultured in vitro can produce a large number of DCs, as well as immature DCs, in high purity. The described in vitro culture method lays a foundation for further investigations of anti-tumor vaccines.

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Stress-activated Dendritic Cells (DC) Induce Dual Interleukin (IL)-15- and IL1β-mediated Pathways, Which May Elicit CD4+ Memory T Cells and Interferon (IFN)-stimulated Genes

Cited by 10 publications

References 62 publications

The Effect of Cellular Stress on T and B Cell Memory Pathways in Immunized and Unimmunized BALB/c Mice

The Effect of Cellular Stress on T and B Cell Memory Pathways in Immunized and Unimmunized BALB/c Mice

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

Culture and Identification of Mouse Bone Marrow-Derived Dendritic Cells and Their Capability to Induce T Lymphocyte Proliferation

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