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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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Journal ArticleDOI

Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions.

TL;DR: Findings show that both T cell and DC persistence in vivo is dependent on CD40‐CD154 interactions, and the profound impact of CD154 deficiency on cell‐mediated immunity may be due to its ability to limit the duration of antigen presentation in vivo and cause the premature demise of antigen‐specific T cells.
Journal ArticleDOI

CD40-CD40 Ligand-Independent Activation of CD8+ T Cells Can Trigger Allograft Rejection

TL;DR: It is concluded that CD40L is not an important costimulatory molecule for CD8+ T cell activation and that following transplantation donor APC can activate recipient CD8- T cells directly without first being primed by CD4+ T cells.
Journal ArticleDOI

Comparative Analysis of Genetically Modified Dendritic Cells and Tumor Cells as Therapeutic Cancer Vaccines

TL;DR: It is found that vaccination with bone marrow–derived DCs engineered to express MAGE-1 via adenoviral-mediated gene transfer led to a dramatic decrease in the number of metastases in a lung metastasis model, and led to prolonged survival and some long-term cures in a subcutaneous preexisting tumor model.
Journal ArticleDOI

Enhancement of Human Cord Blood CD34+ Cell-Derived NK Cell Cytotoxicity by Dendritic Cells

TL;DR: Two culture systems in which human cord blood CD34+ cells from the same donor were induced to generate NK cells and DCs suggest that DCs enhance NK cell cytotoxicity by up-regulating both perforin/granzyme B- and FasL/Fas-based pathways.
Journal ArticleDOI

A member of the dendritic cell family that enters B cell follicles and stimulates primary antibody responses identified by a mannose receptor fusion protein.

TL;DR: Evidence is provided that a subset of DCs enters primary follicles, armed with the capacity to attract and provide antigenic stimulation for T and B lymphocytes, after a primary immunization.
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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