Journal ArticleDOI
Help for cytotoxic-T-cell responses is mediated by CD40 signalling
Sally R.M. Bennett,Sally R.M. Bennett,Francis R. Carbone,Freda Karamalis,Freda Karamalis,Richard A. Flavell,Jacques F. A. P. Miller,William R. Heath +7 more
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TLDR
It is shown that signalling through CD40 on the antigen-presenting cells can replace the requirement for TH cells, indicating that T-cell ‘help’, at least for generation of CTLs by cross-priming, is mediated by signalling throughCD40 onThe antigen- presenting cell.Abstract:
Cytotoxic T lymphocytes (CTLs) which carry the CD8 antigen recognize antigens that are presented on target cells by the class I major histocompatibility complex. CTLs are responsible for the killing of antigen-bearing target cells, such as virus-infected cells. Although CTL effectors can act alone when killing target cells, their differentiation from naive CD8-positive T cells is often dependent on ‘help’ from CD4-positive helper T (TH) cells1,2,3,4. Furthermore, for effective CTL priming, this help must be provided in a cognate manner, such that both the TH cell and the CTL recognize antigen on the same antigen-presenting cell2,4. One explanation for this requirement is that TH cells are needed to convert the antigen-presenting cell into a cell that is fully competent to prime CTL5. Here we show that signalling through CD40 on the antigen-presenting cells can replace the requirement for TH cells, indicating that T-cell ‘help’, at least for generation of CTLs by cross-priming, is mediated by signalling through CD40 on the antigen-presenting cell.read more
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Journal ArticleDOI
Immunobiology of Dendritic Cells
Jacques Banchereau,Francine Brière,Christophe Caux,Jean Davoust,Serge Lebecque,Yong-Jun Liu,Bali Pulendran,Karolina Palucka +7 more
TL;DR: Dendritic cells are antigen-presenting cells with a unique ability to induce primary immune responses and may be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response.
Journal ArticleDOI
Central Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance
TL;DR: This review addresses the heterogeneity of TCM and TEM, their differentiation stages, and the current models for their generation and maintenance in humans and mice.
Journal ArticleDOI
Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
Allan J. Zajac,Joseph N. Blattman,Kaja Murali-Krishna,David J. D. Sourdive,M. Suresh,John D. Altman,Rafi Ahmed +6 more
TL;DR: The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancingCD8 T cell immunity in chronically infected hosts.
Journal ArticleDOI
Antigen Presentation and T Cell Stimulation by Dendritic Cells
TL;DR: Dendritic cells take up antigens in peripheral tissues, process them into proteolytic peptides, and load these peptides onto major histocompatibility complex (MHC) class I and II molecules, thus initiating antigen-specific immune responses, or immunological tolerance.
Journal ArticleDOI
In Vivo Depletion of CD11c+ Dendritic Cells Abrogates Priming of CD8+ T Cells by Exogenous Cell-Associated Antigens
Steffen Jung,Derya Unutmaz,Phillip Wong,Gen Ichiro Sano,Kenia De Los Santos,Tim Sparwasser,Shengji Wu,Sri Vuthoori,Kyung Ko,Fidel Zavala,Eric G. Pamer,Dan R. Littman,Richard A. Lang +12 more
TL;DR: A novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo is reported and it is shown that in vivo DC are required to cross-prime CTL precursors.
References
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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
The immune responses in CD40-deficient mice: Impaired immunoglobulin class switching and germinal center formation
Tsutomu Kawabe,Tetsuji Naka,Kanji Yoshida,Takashi Tanaka,Hiroshi Fujiwara,Sachiko Suematsu,Nobuaki Yoshida,Tadamitsu Kishimoto,Hitoshi Kikutani +8 more
TL;DR: It is suggested that CD40 is essential for T cell-dependent immunoglobulin class switching and germinal center formation, but not for in vivo Tcell-dependent IgM responses and T cell -independent antibody responses.
Journal ArticleDOI
Mice deficient for the CD40 ligand.
Jianchao Xu,Teresa M. Foy,Jon D. Laman,Eileen A. Elliott,Jonathan J. Dunn,Thomas J. Waldschmidt,Jennifer Elsemore,Noelle Randolph J,Richard A. Flavell +8 more
TL;DR: The study confirms the important role of CD40-CD40L interactions in thymus-dependent humoral immune responses and germinal center formation and indicates an inability to develop memory B cell responses.
Journal ArticleDOI
Induction of a CD8( ) cytotoxic T lymphocyte response by cross-priming requires cognate CD4( ) T cell help
Sally R.M. Bennett,Francis R. Carbone,Freda Karamalis,Jacques F. A. P. Miller,William R. Heath +4 more
TL;DR: It is shown that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells, and it is argued that the cognitive nature of this event suggests that theCD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.
Journal ArticleDOI
CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40.
TL;DR: In this article, CD40 ligand-transfected cells provided a potent costimulus for monocyte TNF-alpha and IL-6 production in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-3, or IFN-gamma.