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.
Reads0
Chats0
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.read more
Citations
More filters
Journal ArticleDOI
Enhancement of tumoricidal activity of alveolar macrophages via CD40-CD40 ligand interaction.
Kazuyoshi Imaizumi,Tsutomu Kawabe,Satoshi Ichiyama,Hitoshi Kikutani,Hideo Yagita,Kaoru Shimokata,Yoshinori Hasegawa +6 more
TL;DR: The results suggest that CD40L gene transfer into tumor cells may induce antitumor immunity in a tumor-bearing host and may offer a new strategy for cancer gene therapy.
Journal ArticleDOI
LIGHT regulates CD86 expression on dendritic cells through NF-κB, but not JNK/AP-1 signal transduction pathway
Gang Ming Zou,Wen-Yang Hu +1 more
TL;DR: It is demonstrated that LIGHT regulates CD86 expression through NF‐κB signal transduction pathway but neither p44/42 MAPK nor JNK/AP‐1 signaling pathway, and plays a key role in LIGHT‐mediated upregulation ofCD86 expression.
Journal ArticleDOI
Signaling through NOD-2 and TLR-4 Bolsters the T cell Priming Capability of Dendritic cells by Inducing Autophagy
Nargis Khan,Aurobind Vidyarthi,Susanta Pahari,Shikha Negi,Mohammad Aqdas,Sajid Nadeem,Tapan Agnihotri,Javed N. Agrewala +7 more
TL;DR: This study signifies that NOD-2 and TLR-4 exhibit synergism in invigorating the activity of DCs and this strategy may have significant immunotherapeutic potential in bolstering the function ofDCs and thus improving the immunity against pathogens.
Journal ArticleDOI
Clinical implications of antigen transfer mechanisms from malignant to dendritic cells: Exploiting cross-priming
Ainhoa Arina,Iñigo Tirapu,Carlos Alfaro,Mercedes Rodríguez-Calvillo,Guillermo Mazzolini,Susana Inogés,Ascensión López,Esperanza Feijoo,Maurizio Bendandi,Ignacio Melero +9 more
TL;DR: In this paper, Dendritic cells (DC) are used to transfer antigen from malignant cells to MHC class I molecules expressed on APC and the final outcome of DC cross-presentation could be T-cell activation (cross-priming) but also, and importantly, Tcell tolerance contingent upon the activation/maturation status of DC.
Journal ArticleDOI
Alphaviral Vector-Transduced Dendritic Cells are Successful Therapeutic Vaccines against neu-Overexpressing Tumors in Wild-Type Mice
Timothy P. Moran,Joseph E. Burgents,Brian Long,Ivana R. Ferrer,Elizabeth M. Jaffee,Roland Tisch,Robert E. Johnston,Jonathan S. Serody +7 more
TL;DR: It is demonstrated that VRP-DC vaccines induce potent immunity against established tumors, and the importance of the generation of both CD4(+) T cell and B cell responses for efficient tumor inhibition is emphasized.
References
More filters
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
Chyi-Song Hsieh,Steven E. Macatonia,Catherine S. Tripp,Stanley F. Wolf,Anne O'Garra,Kenneth M. Murphy +5 more
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.
Roberto Manetti,Paola Parronchi,Maria Grazia Giudizi,Marie-Pierre Piccinni,Enrico Maggi,Giorgio Trinchieri,Sergio Romagnani +6 more
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.