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Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.

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TLDR
It is found that ligation of CD40 by CD40L triggers the production of extremely high levels of bioactive IL-12, which is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs.
Abstract
We investigated the possibility that T helper cells might enhance the stimulatory function of dendritic cells (DCs). We found that ligation of CD40 by CD40L triggers the production of extremely high levels of bioactive IL-12. Other stimuli such as microbial agents, TNF-alpha or LPS are much less effective or not at all. In addition, CD40L is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs. These effects of CD40 ligation result in an increased capacity of DCs to trigger proliferative responses and IFN-gamma production by T cells. These findings reveal a new role for CD40-CD40L interaction in regulating DC function and are relevant to design therapeutic strategies using cultured DCs.

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Viral abrogation of stem cell transplantation tolerance causes graft rejection and host death by different mechanisms

TL;DR: It is concluded that a noncytopathic viral infection at the time of transplantation can prevent engraftment of allogeneic bone marrow and result in the death of sublethally irradiated mice treated with costimulation blockade.
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Characteristics and clinical trial results of agonistic anti‑CD40 antibodies in the treatment of malignancies (Review)

Da-Ke Li, +1 more
- 31 Aug 2020 - 
TL;DR: In this article, a review aimed to provide updated details of the clinical results of these agonists, and offer information to further investigate the strategies of combining CD40 activation with chemotherapy, radiotherapy, targeted therapy and immunomodulators.
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Involvement of p38 mitogen-activated protein Kinase in the induction of interleukin-12 p40 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid

TL;DR: Berberine is suggested as an immunotherapeutic compound for induction of IL-12, which is potentially applicable for tumors, infectious disease, and airway inflammation.
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Th cell-independent immune responses to chimeric hemagglutinin/simian human immunodeficiency virus-like particles vaccine.

TL;DR: A novel adjuvant role of influenza HA as well as a new strategy to develop more effective therapeutic vaccines for AIDS patients with low CD4+ T cell counts are suggested.
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GM-CSF-induced regulatory T cells selectively inhibit anti-acetylcholine receptor-specific immune responses in experimental myasthenia gravis.

TL;DR: In this paper, the authors explored the critical role of induced antigen specific Tregs in the therapeutic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in murine experimental autoimmune myasthenia gravis (EAMG).
References
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Journal ArticleDOI

Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.

TL;DR: Cultured DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones and their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR- mediated antigen uptake.
Journal ArticleDOI

The dendritic cell system and its role in immunogenicity

TL;DR: Dendritic cells are specialized to mediate several physiologic components of immunogenicity such as the acquisition of antigens in tissues, the migration to lymphoid organs, and the identification and activation of antigen-specific T cells.
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Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages

TL;DR: This regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate TH1 phenotype.
Journal ArticleDOI

Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products.

TL;DR: The capacity of DCs to capture and process antigen could be modulated by exogenous stimuli was investigated and it was found that DCs respond to tumor necrosis factor alpha, CD40 ligand, IL-1, and lipopolysaccharide with a coordinate series of changes that include downregulation of macropinocytosis and Fc receptors, disappearance of the class II compartment, and upregulation of adhesion and costimulatory molecules.
Journal ArticleDOI

Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells.

TL;DR: IL-12 and CD16+ cells appear to have inhibitory effects on the development of IL-4-producing cells and to play an inductive role in promoting Th1-like responses.
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