The role of CD40/CD154 interactions in the priming, differentiation, and effector function of helper and cytotoxic T cells

Mackey, Megan A.; Barth, Richard J.; Noelle, Randolph J.

doi:10.1002/jlb.63.4.418

Cited by 197 publications

(139 citation statements)

References 103 publications

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“…Since DC-CK1 probably exerts its adjuvant effect after draining to secondary lymphoid organs, the principal cellular sources of the IL-12 needed for the adjuvant activity of DC-CK1 are probably dendritic cells that have migrated from the periphery to the T cell areas of secondary lymphoid organs after Ag uptake. Many studies suggest that IL-12 production by dendritic cells requires CD40-CD40L interaction between dendritic cells and activated T cells (37)(38)(39)(40); however, our results indicate that such an interaction is not required for the IL-12-dependent adjuvant effect of DC-CK1. A possible explanation for this CD40 independence comes from a study by Reis e Sousa et al (46), who showed that in vivo microbial stimulation induces CD40-CD40L-independent IL-12 production by dendritic cells as well as dendritic cell redistribution to T cell areas of secondary lymphoid organs where they initiate primary immune responses.…”

Section: Discussioncontrasting

confidence: 78%

“…It is known that optimal IL-12 production by APCs during the induction of Th1-polarized T cell responses requires engagement of the APC's CD40 molecules by the CD40 ligand (CD40L) molecules of activated T cells (37)(38)(39)(40). To determine whether the adjuvant activity of DC-CK1 requires such signaling, we immunized mice deficient in CD40 along with WT controls with AdPyCS with or without AdDC-CK1, and 2 wk later we measured the CS-specific, CD8 ϩ T cell response by ELISPOT.…”

Section: Dc-ck1 Fails To Enhance Malaria Vaccine-elicited Cd8 ϩ T Celmentioning

confidence: 99%

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The Dendritic Cell-Specific Chemokine, Dendritic Cell-Derived CC Chemokine 1, Enhances Protective Cell-Mediated Immunity to Murine Malaria

Bruña–Romero

Schmieg

Val

et al. 2003

The Journal of Immunology

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Cell-mediated immunity plays a crucial role in the control of many infectious diseases, necessitating the need for adjuvants that can augment cellular immune responses elicited by vaccines. It is well established that protection against one such disease, malaria, requires strong CD8+ T cell responses targeted against the liver stages of the causative agent, Plasmodium spp. In this report we show that the dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1 (DC-CK1), which is produced in humans and acts on naive lymphocytes, can enhance Ag-specific CD8+ T cell responses when coadministered with either irradiated Plasmodium yoelii sporozoites or a recombinant adenovirus expressing the P. yoelii circumsporozoite protein in mice. We further show that these enhanced T cell responses result in increased protection to malaria in immunized mice challenged with live P. yoelii sporozoites, revealing an adjuvant activity for DC-CK1. DC-CK1 appears to act preferentially on naive mouse lymphocytes, and its adjuvant effect requires IL-12, but not IFN-γ or CD40. Overall, our results show for the first time an in vivo role for DC-CK1 in the establishment of primary T cell responses and indicate the potential of this chemokine as an adjuvant for vaccines against malaria as well as other diseases in which cellular immune responses are important.

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Section: Discussioncontrasting

confidence: 78%

Section: Dc-ck1 Fails To Enhance Malaria Vaccine-elicited Cd8 ϩ T Celmentioning

confidence: 99%

The Dendritic Cell-Specific Chemokine, Dendritic Cell-Derived CC Chemokine 1, Enhances Protective Cell-Mediated Immunity to Murine Malaria

Bruña–Romero

Schmieg

Val

et al. 2003

The Journal of Immunology

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“…Induction of anergy rather than deletion may also occur in the absence of CD40 ligation, although in the system described in this work, this was not observed. The necessity for inflammatory signals, such as CD40 activation, to drive productive CD4 and Ab responses has been previously demonstrated (47)(48)(49). In the case of those CD8 T cell responses that require CD4 T cell help, it is known that CD40-mediated activation of APC or virus infection of APC can bypass the CD4 T cell requirement (11)(12)(13).…”

Section: Discussionmentioning

confidence: 96%

Soluble Antigen and CD40 Triggering Are Sufficient to Induce Primary and Memory Cytotoxic T Cells

Lefrançois

Altman

Williams

et al. 2000

The Journal of Immunology

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The signals directing induction of tolerance rather than immunity are largely unknown. The CD8 T cell response to soluble Ags generally results in deletional tolerance following transient, costimulation-dependent activation. We demonstrated that CD40 signaling reversed the outcome of this response. Adoptive transfer of OVA-specific CD8 T cells followed by soluble OVA immunization resulted in induction of lytic activity and optimal clonal expansion only when CD40 was triggered via an agonistic mAb. Activation of CD8 T cells by CD40 signaling was indirect, because CD40 expression by host cells was required. CD40 signaling along with soluble Ag immunization also induced expansion of secondary lymphoid and intestinal mucosal endogenous OVA-specific CD8 T cells as detected by MHC tetramer reactivity. When CD40 activation was included, long-lived secondary lymphoid and mucosal memory CD8 cells were generated from adoptively transferred and endogenous CD8 T cells. Mucosal and peripheral CD8 memory cells exhibited constitutive Ag-specific lytic activity, with mucosal memory cells being 10-fold more lytic than splenic or lymph node memory cells. These results demonstrated that CD40 signaling during a response to a poorly immunogenic soluble Ag was necessary and sufficient for CTL and memory T cell induction.

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“…We found that CD40 expression was significantly increased on the surface of DC after RNAi-inhibited IL-10 expression. A previous report indicated that allogeneic T helper and cytotoxic T cell responses were diminished in CD40 ligand (CD40L)-deficient mice despite the fact that injected DC expressed high levels of MHC class II, B7.1, and B7.2 [23]. CD40 and CD40L interactions play important roles in the priming, differentiation and effector function of helper and cytotoxic T cells [23].…”

Section: Discussionmentioning

confidence: 99%

“…A previous report indicated that allogeneic T helper and cytotoxic T cell responses were diminished in CD40 ligand (CD40L)-deficient mice despite the fact that injected DC expressed high levels of MHC class II, B7.1, and B7.2 [23]. CD40 and CD40L interactions play important roles in the priming, differentiation and effector function of helper and cytotoxic T cells [23]. IL-12 is an inducible cytokine composed of 35-and 40-kDa subunits and is crucial to promoting the development of Th1 cells and cell-mediated immunity [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Small interference RNA modulation of IL‐10 in human monocyte‐derived dendritic cells enhances the Th1 response

Liu

Akasaki

et al. 2004

Eur J Immunol

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RNA interference technology has been used to modulate dendritic cell (DC) function by targeting the expression of genes such as IL-12 and NF-kB. In this paper, we demonstrate that transfection of DC with IL-10-specific double strands of small interference RNA (siRNA) resulted in potent suppression of IL-10 gene expression without inducing DC apoptosis or blocking DC maturation. Inhibition of IL-10 by siRNA was accompanied by increased CD40 expression and IL-12 production after maturation, which endowed DC with the ability to significantly enhance allogeneic T cell proliferation. IL-10 siRNA transfection did not affect MHC class II, CD86, CD83, or CD54 expression in mature DC. To further test the ability of IL-10 siRNA-treated DC to induce a T cell response, naive CD4 T cells were stimulated by autologous DC pulsed with KLH. The results indicated that IL-10 siRNA-transfected DC enhanced Th1 responses by increasing IFN-+ and decreasing IL-4 production. These findings suggest the potential for a novel immunotherapeutic strategy of using IL-10 siRNAtransfected antigen-presenting cells as vaccine delivery agents to boost the Th1 response against pathogens and tumors that are controlled by Th1 immunity.

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The role of CD40/CD154 interactions in the priming, differentiation, and effector function of helper and cytotoxic T cells

Cited by 197 publications

References 103 publications

The Dendritic Cell-Specific Chemokine, Dendritic Cell-Derived CC Chemokine 1, Enhances Protective Cell-Mediated Immunity to Murine Malaria

The Dendritic Cell-Specific Chemokine, Dendritic Cell-Derived CC Chemokine 1, Enhances Protective Cell-Mediated Immunity to Murine Malaria

Soluble Antigen and CD40 Triggering Are Sufficient to Induce Primary and Memory Cytotoxic T Cells

Small interference RNA modulation of IL‐10 in human monocyte‐derived dendritic cells enhances the Th1 response

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