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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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An immunostimulatory oligodeoxynucleotide containing a cytidine-guanosine motif protects senescence-accelerated mice from lethal influenza virus by augmenting the T helper type 1 response.

TL;DR: The results suggest that CpG ODN could contribute to the development of a protective strategy against infectious diseases, especially among immunocompromised elderly persons, by stimulating Th1 immune responses.
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Role of IL-12 in Staphylococcus aureus-triggered arthritis and sepsis.

TL;DR: It is demonstrated that endogenous production of IL-12 is crucial for survival in Staphylococcus aureus-induced arthritis in mice, and IL- 12-deficient mice were exposed to higher staphylitis load but demonstrated no increased severity of arthritis.
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Mechanisms of dendritic cell-based vaccination against infection.

TL;DR: It is demonstrated that DC, once properly conditioned ex vivo, mediate complete and durable protection against infection, and the necessity to define the mechanisms responsible for the immunostimulatory capacity of DC in vivo is discussed.
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In Vivo Antitumor Effect of CD40L-transduced Tumor Cells as a Vaccine for B-Cell Lymphoma

TL;DR: The results show that genetic modification of tumor B cells with CD40L can be a useful strategy to promote systemic immunity against B-cell malignancies and provide an in vivo system to allow for additional evaluation and refinement of this approach.
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Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets

TL;DR: Although several features of the DC network are conserved between humans and mice, the expression of several toll-like receptors as well as the production of cytokines that regulate T-cell differentiation are different.
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.
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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.
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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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