scholarly journals Cytotoxic and antigen presenting functions of T helper-1-activated dendritic cells

2012 ◽  
Vol 1 (4) ◽  
pp. 566-568 ◽  
Author(s):  
Nicolas Larmonier ◽  
Bernard Bonnotte ◽  
Emmanuel Katsanis
2009 ◽  
Vol 125 (2) ◽  
pp. 114-118 ◽  
Author(s):  
Ildelfonso Vicente-Suarez ◽  
Jason Brayer ◽  
Alejandro Villagra ◽  
Fengdong Cheng ◽  
Eduardo M. Sotomayor

2021 ◽  
Vol 10 (12) ◽  
pp. 2578
Author(s):  
Masutaka Furue ◽  
Mihoko Furue

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis.


Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Naoki Tokumasa ◽  
Akira Suto ◽  
Shin-ichiro Kagami ◽  
Shunsuke Furuta ◽  
Koichi Hirose ◽  
...  

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.


PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e44266 ◽  
Author(s):  
Felix S. Lichtenegger ◽  
Katharina Mueller ◽  
Bettina Otte ◽  
Barbara Beck ◽  
Wolfgang Hiddemann ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2878-2885 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Scott Barbuto ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
Amitabha Mazumder ◽  
...  

Abstract IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.


1994 ◽  
Vol 179 (1) ◽  
pp. 249-258 ◽  
Author(s):  
K M Gilbert ◽  
W O Weigle

Antigen presentation by resting splenic B cells has been shown previously to induce T helper 1 cell (Th1) anergy. In contrast to expectations, it was found here that B cells treated with F(ab')2 goat anti-mouse immunoglobulin (IgM) for 24 or 48 h also presented antigen (Ag) to Th1 cells in a manner that induced dramatic Ag-specific proliferative inactivation. The tolerogenicity of the anti-Ig-treated B cells was consistent with the observation that these B cells were only slightly more efficient than resting B cells in stimulating human gamma globulin (HGG)-induced proliferation of HGG-specific Th1 cells in primary cultures. The activated B cells were, however, more efficient than resting B cells in stimulating a primary mixed leukocyte reaction, and exhibited increased expression of major histocompatibility complex class II molecules, RL388 Ag and transferrin receptor. In addition, unlike resting B cells, which expressed little detectable B7, anti-Ig-treated B cells expressed high levels of B7. The functional capacity of the B7 expressed on the activated B cells was demonstrated by the fact that the Ag-presenting capacity of these B cells was inhibited by the addition to culture of CTLA4Ig, a soluble receptor for B7. It is unlikely that the tolerogenicity of the activated B cells was due to an inability of the Th1 cells to respond to B7 signals; the Th1 clones used in the experiments, unlike the Th2 clones tested, expressed CD28, the ligand for B7. In addition, anti-CD28 monoclonal antibody inhibited the induction of Th1 cell anergy when added to cultures of Th1 cells and Ag-pulsed fixed antigen-presenting cells. Taken together, the results indicate that B cells, even when activated, do not satisfy the costimulatory requirements of the Th1 cells used here, and therefore can present Ag in a tolerogenic fashion to Th1 cells. The costimulator deficiency of activated B cells may reflect an inadequacy in the level of B7 expressed or a lack of some other molecule.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3873-3873
Author(s):  
Godfrey ChiFung Chan ◽  
W.K. Chan ◽  
H.K. Law ◽  
Z.B. Lin ◽  
Y.L. Lau

Abstract Background: Purified polysaccharides extracted from plants and fungi have been shown to induce immune responses in-vivo and vitro over the past decade. Currently, most of these polysaccharides are found to be glucan but with different branch structure and sizes. Their relative potency and effect on human immune cells remains unknown. This study aims to compare their relative effect on human dendritic cell, the most potent antigen presenting cell. Materials & Methods: We selected 2 prototypes of purified polysaccharides extracted from: 1) Ganoderma lucidum (GL, Lingzhi, Reishi) mycelium, a widely used herb with long and branching β (1® 3), (1® 6) glucan structure (provided by Prof. Lin ZB, Beijing) and 2) Barley with shorter and different branching β (1® 3), (1® 4) structure (provided by Prof. Cheung VNK, NY). Their characteristics and chemical properties had been reported previously. Human peripheral blood mononuclear cells (PBMCs) proliferation was studied by XTT assay. Human dendritic cells (DCs) were derived from monocytes and maturation of DCs were determined by: a) immunophenotypic shift using flow cytometer; 2) dextran endocytosis assay and 3) mixed lymphocytes reaction. Cytokine secretions were determined by ELISA test. Comparisons between means were by nonparametric Student’s t test (2-tailed). Results: We found that purified polysaccharides from GL but not barley could induce PBMCs proliferation and maturation of DCs. GL polysaccharides could enhance phenotypic and functional maturation of DCs with significant IL-12 and IL-10 production. DCs were relatively inert to Barley glucans stimulation. However, both polysaccharides did not polarize T cells into the direction of T helper 1, T helper 2 or regulatory T cells. Conclusions: Our study shown that purified polysaccharides extracted from plants and fungi have different effect on human DCs and their potency and effects are probably affected by their respective sources and structures.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Seunga Choi ◽  
Han-Gyu Choi ◽  
Ki-Won Shin ◽  
Yong Woo Back ◽  
Hye-Soo Park ◽  
...  

The attenuated vaccineMycobacterium bovisBCG (Bacille Calmette Guerin) has limited protective efficacy against TB. The development of more effective TB vaccines has focused on the mycobacterial antigens that cause strong T helper 1 (Th1) responses. Mtb protein Rv3841 (bacterioferritin B; BfrB) is known to play a crucial role in the growth of Mtb. Nonetheless, it is unclear whether Rv3841 can induce protective immunity against Mtb. Here, we studied the action of Rv3841 in maturation of dendritic cells (DCs) and its engagement in the development of T-cell immunity. We found that Rv3841 functionally activated DCs by upregulating costimulatory molecules and increased secretion of proinflammatory cytokines. Activation of DCs by Rv3841 was mediated by Toll-like receptor 4 (TLR4), followed by triggering of mitogen-activated protein kinase and nuclear factor-κB signaling pathways. In addition, Rv3841-matured DCs effectively proliferated and polarized Th1 immune response of naïve CD4+and CD8+T-cells. Moreover, Rv3841 specifically caused the expansion of CD4+CD44highCD62LlowT-cells from Mtb-infected mice; besides, the T-cells activated by Rv3841-matured DCs inhibited intracellular mycobacterial growth. Our data suggest that Rv3841 induces DC maturation and protective immune responses, a finding that may provide candidate of effective TB vaccines.


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