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Open AccessJournal ArticleDOI

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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Journal ArticleDOI

Dendritic cell maturation and antigen presentation in the absence of invariant chain

TL;DR: It is reported that DCs derived from Ii -/- H2(k) but not Ii-/- H 2(b) mice undergo normal maturation in response to tumor necrosis factor alpha and show a high degree of class II surface expression, which supports the existence of Io-independent molecular requirements for class II transport and peptide loading in DCs.
Patent

Anti-cd40 antibodies and methods of use

TL;DR: In this article, high affinity anti-CD40 monoclonal antibodies and related compositions can be used in any of a variety of therapeutic methods for the treatment of cancer and other diseases.
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The taming of IL-12: suppressing the production of proinflammatory cytokines.

TL;DR: This review focuses on the production of IL‐12 by antigen‐presenting cells and the methods by which the down‐regulation ofIL‐12 production can be exploited either by pathogens or for therapeutic ends.
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HIV-1-Specific CTL Responses Primed In Vitro by Blood-Derived Dendritic Cells and Th1-Biasing Cytokines

TL;DR: The results suggest that this in vitro vaccine model may be useful in identifying immunogenic epitopes as vaccine targets and in evaluating the effects of cytokines and other adjuvants on Ag-specific T cell induction.
Journal ArticleDOI

Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type-1 immunity by licensing host dendritic cells to produce IL-12

TL;DR: It is demonstrated that NK1R signaling activates therapeutic DCs capable of biasing type 1 immunity by inhibition of interleukin-10 synthesis and secretion, without affecting their low levels of IL-12 production.
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.
Journal ArticleDOI

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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