scholarly journals Thymic DCs derived IL-27 regulates the final maturation of CD4+ SP thymocytes

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hui Tang ◽  
Jie Zhang ◽  
Xiuyuan Sun ◽  
Xiaoping Qian ◽  
Yu Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Receptor Expression ◽  
Thymocyte Development ◽  
Final Maturation ◽  
Single Positive ◽  
Th17 Differentiation

Abstract IL-27, as a pleiotropic cytokine, promotes the differentiation of naïve T cells to Th1, while suppressing Th2 and Th17 differentiation in the periphery. However, the role of IL-27 in the thymocyte development remains unknown. Here we showed that IL-27 was highly expressed in thymic plasmacytoid dendritic cells (pDCs) while its receptor expression was mainly detected in CD4+ single-positive (SP) thymocytes. Deletion of the p28 subunit in DCs resulted in a reduction of the most mature Qa-2+ subsets of CD4+ SP T cells. This defect was rescued by intrathymic administration of exogenous IL-27. In vitro differentiation assay further demonstrated that IL-27 alone was able to drive the maturation of the newly generated 6C10+CD69+CD4+ SP cells into Qa-2+ cells. Collectively, this study has revealed an important role of thymic DCs-derived IL-27 in the regulation of the phenotypic maturation of CD4+ SP thymocytes.

scholarly journals Eminent role of ICOS costimulation for T cells interacting with plasmacytoid dendritic cells

Immunology ◽  
2006 ◽  
Vol 118 (3) ◽  
pp. 353-360 ◽  
Author(s):  
Marko Janke ◽  
Esther J. Witsch ◽  
Hans W. Mages ◽  
Andreas Hutloff ◽  
Richard A. Kroczek
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

scholarly journals T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masaru Shimizu ◽  
Yuya Kondo ◽  
Reona Tanimura ◽  
Kotona Furuyama ◽  
Masahiro Yokosawa ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
T Helper 1 ◽  
Collagen Induced Arthritis ◽  
Over Expression ◽  
Th17 Differentiation ◽  
And Function ◽  
Arthritic Joints

AbstractT-bet is a key transcription factor for the T helper 1 lineage and its expression level is negatively correlated to inflammation in patients with rheumatoid arthritis (RA). Our previous study using T-bet transgenic mice revealed over-expression of T-bet completely suppressed collagen-induced arthritis (CIA), a murine model of RA, indicating a potential suppressive role of T-bet in the pathogenesis of autoimmune arthritis. Here, we show T-bet-deficiency exacerbated CIA. T-bet in CD4 + T cells, but not in CD11c + dendritic cells, was critical for regulating the production of IL-17A, IL-17F, IL-22, and TNFα from CD4 + T cells. T-bet-deficient CD4 + T cells showed higher RORγt expression and increased IL-17A production in RORγt-positive cells after CII immunization. In addition, T-bet-deficient naïve CD4 + T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-betfl/fl (cKO) mice was more severe and T-bet-deficient CD4 + T cells in the arthritic joints of cKO mice showed higher RORγt expression and increased IL-17A production. Transcriptome analysis of T-bet-deficient CD4 + T cells revealed that expression levels of Th17-related genes were selectively increased. Our results indicate that T-bet in CD4 + T cells repressed RORγt expression and function resulting in suppression of arthritogenic Th17 cells and CIA.

scholarly journals Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina modulates the functions of chicken dendritic cells to boost Th1 type immune response and stimulates autologous CD4+ T cells differentiation in-vitro

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Shakeel Ahmed Lakho ◽  
Muhammad Haseeb ◽  
Jianmei Huang ◽  
Zhang Yang ◽  
Muhammad Waqqas Hasan ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immunoblot Analysis ◽  
Eimeria Acervulina ◽  
Ifn Γ ◽  
Negative Controls ◽  
Th1 Polarization ◽  
Dc Maturation

AbstractDendritic cells (DCs) play a pivotal role to amplify antigen-specific immune responses. Antigens that sensitize T cells via antigen-presentation by DCs could enhance the capacity of host immunity to fight infections. In this study, we tested the immunogenic profiles of chicken DCs towards Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina (EaGAPDH). Immunoblot analysis showed that recombinant EaGAPDH (rEaGAPDH) protein was successfully recognized by rat sera generated against rEaGAPDH. Interaction and internalisation of rEaGAPDH by chicken splenic-derived DCs (chSPDCs) was confirmed by immunofluorescence analysis. Flow cytometry revealed that chSPDCs upregulated MHCII, CD1.1, CD11c, CD80, and CD86 cell-surface markers. Moreover, mRNA expressions of DC maturation biomarkers (CCL5, CCR7, and CD83) and TLR signalling genes (TLR15 and MyD88) were also upregulated whereas those of Wnt signalling were non-significant compared to negative controls. rEaGAPDH treatment induced IL-12 and IFN-γ secretion in chSPDCs but had no effect on IL-10 and TGF-β. Likewise, DC-T cell co-culture promoted IFN-γ secretion and the level of IL-4 was unaffected. Proliferation of T cells and their differentiation into CD3+/CD4+ T cells were triggered in chSPDCs-T cells co-culture system. Taken together, rEaGAPDH could promote Th1 polarization by activating both host DCs and T cells and sheds new light on the role of this important molecule which might contribute to the development of new DCs-based immunotherapeutic strategies against coccidiosis.

scholarly journals Essential role of the interleukin 2-interleukin 2 receptor pathway in thymocyte maturation in vivo.

1988 ◽  
Vol 168 (5) ◽  
pp. 1741-1747 ◽  
Author(s):  
L Tentori ◽  
D L Longo ◽  
J C Zuñiga-Pflucker ◽  
C Wing ◽  
A M Kruisbeek
Keyword(s):  
T Cells ◽  
Essential Role ◽  
Interleukin 2 ◽  
Beta Chain ◽  
Thymocyte Development ◽  
Single Positive ◽  
Thymocyte Differentiation ◽  
Single Positive Cell

The role of the IL-2-IL-2-R pathway in thymocyte differentiation in vivo is unknown. We have examined fetal thymocyte development in vivo, under conditions where all IL-2-R were saturated from day 13 of gestation with anti-IL-2-R mAbs that were previously shown to render mature T cells unable to respond to IL-2. This produced a dramatic change in the composition of developing T cells: thymocytes from day 1 neonatal mice born to anti-IL-2-R-treated mothers did not contain CD4+ or CD8+ single-positive cell populations. In addition, no generation of surface TCR beta chain-expressing T cells or antigen-reactive functional T cells occurred in treated mice. These data suggest that IL-2-IL-2-R interactions provide signals crucial to in vivo intrathymic development of mature T cells.

scholarly journals Role of plasmacytoid dendritic cells and inducible costimulator‐positive regulatory T cells in the immunosuppression microenvironment of gastric cancer

2014 ◽  
Vol 105 (2) ◽  
pp. 150-158 ◽  
Author(s):  
Xiao‐Mei Huang ◽  
Xiao‐Sun Liu ◽  
Xian‐Ke Lin ◽  
Hang Yu ◽  
Jian‐Yi Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Inducible Costimulator

scholarly journals The majority of postselection CD4+ single-positive thymocytes requires the thymus to produce long-lived, functional T cells.

1995 ◽  
Vol 181 (1) ◽  
pp. 235-245 ◽  
Author(s):  
R Dyall ◽  
J Nikolić-Zugić
Keyword(s):  
T Cells ◽  
T Cell ◽  
Control Point ◽  
Cell Receptor ◽  
Cross Linking ◽  
Final Maturation ◽  
Tumor Virus ◽  
Single Positive ◽  
Developmental Characteristics

We have previously isolated, and characterized in vitro, two subsets of CD4hi T cell receptor (TCR)hi single positive (SP) thymocytes: CD8- and CD8lo. In this report, we have analyzed phenotypic, functional, and developmental characteristics of these "late" CD4hi SP thymocyte subsets. The TCRhi phenotype and the elimination of T cells expressing TCR V beta segments reactive with endogenous mouse mammary tumor virus (MMTV) products suggested that both subsets had undergone positive and negative selection. CD8-4hi thymocytes were functional, as judged by their ability to: (a) induce lethal graft versus host disease (GVHD); (b) survive and expand in peripheral lymphoid organs; and (c) proliferate, rather than undergo apoptosis, in response to in vitro TCR cross-linking. By contrast, CD8lo4hi cells could not induce GVHD, were unable to expand (and perhaps even survive) in peripheral organs and underwent apoptosis upon TCR cross-linking. However, when reintroduced into the thymus, these cells matured into functional, long-lived CD8-4hi lymphocytes. These results document an obligatory requirement for the thymic microenvironment in the final maturation of the majority of CD4hi SP postselection thymocytes, and demonstrate the existence of a previously unrecognized control point in T cell development.

scholarly journals Noncanonical Wnt signaling promotes apoptosis in thymocyte development

2007 ◽  
Vol 204 (13) ◽  
pp. 3077-3084 ◽  
Author(s):  
Huiling Liang ◽  
Andrew H. Coles ◽  
Zhiqing Zhu ◽  
Jennifer Zayas ◽  
Roland Jurecic ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Wnt Signaling ◽  
T Cell Development ◽  
Cell Development ◽  
Thymocyte Development ◽  
Growth And Survival ◽  
Canonical Wnt

The Wnt–β-catenin signaling pathway has been shown to govern T cell development by regulating the growth and survival of progenitor T cells and immature thymocytes. We explore the role of noncanonical, Wnt–Ca2+ signaling in fetal T cell development by analyzing mice deficient for Wnt5a. Our findings reveal that Wnt5a produced in the thymic stromal epithelium does not alter the development of progenitor thymocytes, but regulates the survival of αβ lineage thymocytes. Loss of Wnt5a down-regulates Bax expression, promotes Bcl-2 expression, and inhibits apoptosis of CD4+CD8+ thymocytes, whereas exogenous Wnt5a increases apoptosis of fetal thymocytes in culture. Furthermore, Wnt5a overexpression increases apoptosis in T cells in vitro and increases protein kinase C (PKC) and calmodulin-dependent kinase II (CamKII) activity while inhibiting β-catenin expression and activity. Conversely, Wnt5a deficiency results in the inhibition of PKC activation, decreased CamKII activity, and elevation of β-catenin amounts in thymocytes. These results indicate that Wnt5a induction of the noncanonical Wnt–Ca2+ pathway alters canonical Wnt signaling and is critical for normal T cell development.

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