CD80 and CD86 Differentially Regulate Mechanical Interactions of T-Cells with Antigen-Presenting Dendritic Cells and B-Cells

Lim, Tong Seng; Goh, James Kang Hao; Mortellaro, Alessandra; Lim, Chwee Teck; Hämmerling, Günter J.; Ricciardi‐Castagnoli, Paola

doi:10.1371/journal.pone.0045185

Cited by 127 publications

(90 citation statements)

References 59 publications

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“…Our data show that after immunization with soluble antigen and double-stranded RNA, Xcr1-expressing migratory DCs that have newly arrived in the SDLN interacted with antigen-specific CD8 + T cells more prominently than other Xcr1-expressing DCs, i.e., LN-resident DCs and the migratory DCs that had arrived in the LNs before immunization. Future studies need to test whether the superior interaction ability is dependent on the prominent upregulation of CD86 and CD80 by the newly arriving migratory DCs, because the costimulatory molecules can strengthen antigendependent interactions between T cells and DCs (27). It is also likely, but not certain, that the newly arriving migratory DCs present the highest amounts of peptides after they have encountered antigen plus double-stranded RNA in the skin.…”

Section: Discussionmentioning

confidence: 99%

Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node

Kitano

Yamazaki

Takumi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

105

108

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Dendritic cells (DCs) are antigen-presenting cells specialized for activating T cells to elicit effector T-cell functions. Cross-presenting DCs are a DC subset capable of presenting antigens to CD8+ T cells and play critical roles in cytotoxic T-cell-mediated immune responses to microorganisms and cancer. Although their importance is known, the spatiotemporal dynamics of cross-presenting DCs in vivo are incompletely understood. Here, we study the T-cell zone in skin-draining lymph nodes (SDLNs) and find it is compartmentalized into regions for CD8 + T-cell activation by cross-presenting DCs that express the chemokine (C motif) receptor 1 gene, Xcr1 and for CD4 + T-cell activation by CD11b + DCs. Xcr1-expressing DCs in the SDLNs are composed of two different populations: migratory (CD103 hi ) DCs, which immigrate from the skin, and resident (CD8α hi ) DCs, which develop in the nodes. To characterize the dynamic interactions of these distinct DC populations with CD8 + T cells during their activation in vivo, we developed a photoconvertible reporter mouse strain, which permits us to distinctively visualize the migratory and resident subsets of Xcr1-expressing DCs. After leaving the skin, migratory DCs infiltrated to the deep T-cell zone of the SDLNs over 3 d, which corresponded to their half-life in the SDLNs. Intravital two-photon imaging showed that after soluble antigen immunization, the newly arriving migratory DCs more efficiently form sustained conjugates with antigen-specific CD8 + T cells than other Xcr1-expressing DCs in the SDLNs. These results offer in vivo evidence for differential contributions of migratory and resident cross-presenting DCs to CD8 + T-cell activation.dendritic cell | CD8 + T cell | cross-presentation | intravital two-photon imaging | photoconversion

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Section: Discussionmentioning

confidence: 99%

Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node

Kitano

Yamazaki

Takumi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

105

108

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“…Primer sequences (Table II) were designed according to GenBank and synthesized by DaAn Gene Co., Ltd. of Sun Yat-Sen University (Guangzhou, China). At 24 h post-transfection, the total RNA of 1x10 6 DCs was extracted using TRIzol reagent (Invitrogen; Thermo Fisher Scientific, Inc.) and reverse transcribed and amplified using QuantiTect SYBR Green RT-PCR kit (Qiagen GmbH, Hilden, Germany) in a Roche LightCycler 480 (Roche Diagnostics, Basel, Switzerland). The amplifications were carried out according to the manufacturer's protocol for the QuantiTect SYBR Green RT-PCR kit (Takala, Japan).…”

Section: Reverse Transcription-quantitative Polymerase Chain Reactionmentioning

confidence: 99%

“…Activation of T cells requires signals which are initiated via the TCR complex and cluster of differentiation (CD) 28. Mature dendritic cells (mDCs) express high levels of the co-stimulatory molecules CD80 and CD86, which provide the signal that is required for triggering T cell activation, expansion and differentiation via interaction with CD28 (6). Previous studies have demonstrated that CD80 and CD86 levels are elevated in patients with asthma (7,8).…”

Section: Introductionmentioning

confidence: 99%

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

Yan

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Dendritic cells (DCs) are associated with the activation and differentiation of T helper (Th) cells. Cluster of differentiation (CD)80 and CD86, the co-stimulatory molecules highly expressed in DCs, have are prominent in promoting the differentiation of Th cells toward Th2 cells. However, little is known about the effect of CD80 and CD86 knockdown on Th1/Th2 cytokine production in mature DCs (mDCs). The aim of the present study was to investigate whether small-interfering RNA (siRNA) could suppress the surface expression of CD80 and CD86 in mDCs. The effects of CD80 and CD86 knockdown in mDCs on Th1/Th2 cytokine expression were examined using an asthmatic murine model. DCs were isolated, separated and cultured in vitro. Flow cytometry was used to examine the expression of CD11c, CD80 and CD86 on the DCs. The DCs were transfected with CD80-and CD86-specific siRNA, while non-siRNA and negative siRNA controls were also designed. Then, the mRNA and protein expression levels of CD80 and CD86 were determined by reverse transcription-quantitative polymerase chain reaction and flow cytometry, respectively. The levels of interferon (IFN)-γ and interleukin (IL)-4 produced by T cells co-cultured with mDCs were measured by enzyme-linked immunosorbent assay. Substantial downregulation of CD80 and CD86 mRNA and protein levels were observed in the mDCs following transfection with siRNA. The level of IFN-γ produced by T cells co-cultured with mDCs was significantly increased in the siRNA group, while IL-4 production was significantly decreased. These results show that specific targeting of CD80 and CD86 with siRNA is able to suppress CD80/CD86 expression and consequently regulate Th1/Th2 cytokine levels by increasing IFN-γ production and decreasing IL-4 levels in an asthmatic murine model.

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“…Furthermore, the expression of distinct molecules associated with B cell activation was evaluated in CD27+IgM+B cells. CD86 is a critical co-stimulatory molecule to facilitate the interaction of T cells with B cells (30). CD95 is a death receptor, which initiates extrinsic pathways of apoptosis to remove activated immune cells (31).…”

Section: Discussionmentioning

confidence: 99%

“…To measure the phenotypic features of peripheral IgM+B cell subsets, 1x10 6 PBMCs were incubated in 200 µl blocking solution consisting of 2% bovine serum albumin (Genview Corp., Houston, TX, USA) in PBS for 30 Following washing twice with PBS, the cells were fixed with 1% paraformaldehyde in the dark at 4˚C for 12 h. Then the expression of surface molecules on cells were assayed using the BD FACSCalibur (BD Biosciences) and data were analyzed using FlowJo 7.6 software (Tree Star, Inc., Ashland, OR, USA). Based on expression of CD5, B cells were divided into CD5+B cells (B1 cells) and CD5-B cells (B2 cells) (20).…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

Abnormal phenotypic features of IgM+B cell subsets in patients with chronic hepatitis C virus infection

Kong

Feng

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Hepatitis C virus (HCV) infection is associated with B cell abnormality; however the phenotypic profiles of immunoglobulin (Ig)M+B cell subsets in patients with HCV infection remain unclear. In the current study, the effect of HCV infection on IgM+B cell subsets was evaluated. The percentages, as well as the differentiation and activation features of peripheral IgM+B naive subsets [cluster of differentiation (CD)27-IgM+B cells] and IgM+B memory subsets (CD27+IgM+B cells) were assessed using flow cytometry in 27 patients with chronic hepatitis C (CHC) and 20 healthy controls (HCs). The frequency of CD27+IgM+B memory subsets detected in patients with CHC was significantly higher than that in HCs (P<0.05). Although the frequency of CD27-IgM+B naive subsets was similar in both groups, there was a significantly higher proportion of CD5+B cells detected in the CD27-IgM+B subsets of patients with CHC compared with HCs (P<0.05). Among CD27-IgM+B subsets, abnormal differentiation was associated with HCV infection, with significantly increased percentages of IgD+B cells and CD38+B cells in patients with CHC compared with HCs (P<0.05). In CD27+IgM+B memory subsets, the abnormality of cell differentiation was associated with a significantly increased percentage of CD38+B cells in patients with CHC compared with HCs (P<0.05). In addition, the percentage of activated CD27+IgM+B subsets in patients with CHC were significantly higher than those observed in HCs (P<0.05). The number of CD27-IgD+IgM+B, CD27-CD38+IgM+B and CD27+CD38+IgM+B cells were negatively correlated with HCV RNA in patients with CHC. These results suggest that HCV infection contributes to abnormalities in the percentage, differentiation and activation of IgM+B cell subsets and may disrupt the immune response mediated by IgM+B cells.

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CD80 and CD86 Differentially Regulate Mechanical Interactions of T-Cells with Antigen-Presenting Dendritic Cells and B-Cells

Cited by 127 publications

References 59 publications

Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node

Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

Abnormal phenotypic features of IgM+B cell subsets in patients with chronic hepatitis C virus infection

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