scholarly journals Alterations of Dendritic Cells in Sepsis: Featured Role in Immunoparalysis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xia Fan ◽  
Zheng Liu ◽  
He Jin ◽  
Jun Yan ◽  
Hua-ping Liang
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Early Stage ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Immune Disorder ◽  
And Function ◽  
Antigen Presenting

Sepsis, the leading cause of mortality in intensive care unit, is characterized by hyperinflammatory response in the early stage and followed by a period of immunosuppression. This immune disorder is believed to be the potent factor that is tightly associated with high mortality in sepsis. Dendritic cells (DCs) serve as professional antigen-presenting cells that play a vital role in immune response by activating T lymphocytes. During the progression of sepsis, DCs have been reported to take part in the aberrant immune response and be necessary for survival. Therefore, a better understanding of the DCs pathology will be undoubtedly beneficial for resolving the problems occurring in sepsis. This review discusses effects of sepsis on DCs number and function, including surface molecules expression, cytokines secretion, and T cell activation, and the underlying mechanism as well as some potential therapeutic strategies.

Measles virus and immunomodulation: molecular bases and perspectives

2002 ◽  
Vol 4 (13) ◽  
pp. 1-18 ◽  
Author(s):  
Sibylle Schneider-Schaulies ◽  
Volker ter Meulen
Keyword(s):  
Immune Response ◽  
T Cell Activation ◽  
Measles Virus ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Decisive Role ◽  
Immune Functions ◽  
Secondary Infections ◽  
And Function ◽  
Antigen Presenting

Measles virus (MV) remains among the most potent global pathogens, killing more than 1 million children annually. The virus induces a profound suppression of immune functions that favours the establishment of, and aggravates the course of, secondary infections. By contrast, MV-specific immune responses are efficiently generated, and these clear the virus from the organism and confer a long-lasting immunity. As sensitisers of pathogen encounter and instructors of the adaptive immune response, professional antigen-presenting cells (APCs) such as dendritic cells play a decisive role in the induction and quality of the MV-specific immune response. However, key features of immune suppression associated with MV are compatible with interference with APC maturation and function, and subsequent qualitative and quantitative alterations of T-cell activation.

scholarly journals Complete differentiation of CD8+ T cells activated locally within the transplanted liver

2006 ◽  
Vol 203 (2) ◽  
pp. 437-447 ◽  
Author(s):  
Ingo Klein ◽  
Ian Nicholas Crispe
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Underlying Mechanism ◽  
Color Flow ◽  
Antigen Presenting ◽  
Transplantation Model

The transplanted liver elicits systemic tolerance, and the underlying mechanism may also account for the persistence of liver infections, such as malaria and viral hepatitis. These phenomena have led to the hypothesis that antigen presentation within the liver is abortive, leading to T cell tolerance or apoptosis. Here we test this hypothesis in an optimized orthotopic liver transplantation model. In direct contradiction to this model, the liver itself induces full CD8+ T cell activation and differentiation. The effects of microchimerism were neutralized by bone marrow transplantation in the liver donor, and the lack of liver-derived antigen-presenting cells was documented by eight-color flow cytometry and by sensitive functional assays. We conclude that local antigen presentation cannot explain liver tolerance. On the contrary, the liver may be an excellent priming site for naive CD8+ T cells.

Inhibition of maturation and function of dendritic cells by intravenous immunoglobulin

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 758-765 ◽  
Author(s):  
Jagadeesh Bayry ◽  
Sébastien Lacroix-Desmazes ◽  
Cedric Carbonneil ◽  
Namita Misra ◽  
Vladimira Donkova ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Intravenous Immunoglobulin ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Activity ◽  
Interleukin 12 ◽  
Immune Mediated ◽  
And Function

Normal immunoglobulin G for therapeutic use (intravenous immunoglobulin [IVIg]) is used in an increasing number of immune-mediated conditions, including acute and chronic/relapsing autoimmune diseases, transplantation, and systemic inflammatory disorders. Several mutually nonexclusive mechanisms of action account for the immunoregulatory effects of IVIg. Although IVIg inhibits T-cell proliferation and T-cell cytokine production, it is unclear whether these effects are directly dependent on the effects of IVIg on T cells or they are dependent through the inhibition of antigen-presenting cell activity. Here, we examined the effects of IVIg on differentiation, maturation, and function of dendritic cells (DCs). We show that IVIg inhibits the differentiation and maturation of DCs in vitro and abrogates the capacity of mature DC to secrete interleukin-12 (IL-12) on activation while enhancing IL-10 production. IVIg-induced down-regulation of costimulatory molecules associated with modulation of cytokine secretion resulted in the inhibition of autoreactive and alloreactive T-cell activation and proliferation. Modulation of DC maturation and function by IVIg is of potential relevance to its immunomodulatory effects in controlling specific immune responses in autoimmune diseases, transplantation, and other immune-mediated conditions.

scholarly journals Expression and functional significance of an additional ligand for CTLA-4

1993 ◽  
Vol 90 (23) ◽  
pp. 11054-11058 ◽  
Author(s):  
D J Lenschow ◽  
G H Su ◽  
L A Zuckerman ◽  
N Nabavi ◽  
C L Jellis ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
T Cell Proliferation ◽  
Antigen Presenting

Effective T-cell activation requires antigen/major histocompatibility complex engagement by the T-cell receptor complex in concert with one or more costimulatory molecules. Recent studies have suggested that the B7 molecule, expressed on most antigen presenting cells, functions as a costimulatory molecule through its interaction with CD28 on T cells. Blocking the CD28/B7 interaction with CTLA4Ig inhibits T-cell activation in vitro and induces unresponsiveness. We demonstrate that another molecule(s), termed B7-2, is expressed constitutively on dendritic cells, is differentially regulated on B cells, and costimulates naive T cells responding to alloantigen. B7-2 is up-regulated by lipopolysaccharide in < 6 hr and is maximally expressed on the majority of B cells by 24 hr. In contrast, B7 is detected only on a subset of activated B cells late (48 hr) after stimulation. In addition, Con A directly induces B7-2 but not B7 expression on B cells. Finally, although both anti-B7 monoclonal antibodies and CTLA4Ig blocked T-cell proliferation to antigen-expressing B7 transfectants, only CTLA4Ig had any significant inhibitory effect on T-cell proliferation to antigens expressed on natural antigen presenting cells, such as dendritic cells. Thus, B7 is not the only costimulatory molecule capable of initiating T-cell responses since a second ligand, B7-2, can provide a necessary second signal for T-cell activation.

CD83-positive dendritic cells are present in occasional perivascular cuffs in multiple sclerosis lesions

2003 ◽  
Vol 9 (2) ◽  
pp. 142-147 ◽  
Author(s):  
J Plumb ◽  
M A Armstrong ◽  
M Duddy ◽  
M Mirakhur ◽  
S McQuaid
Keyword(s):  
Multiple Sclerosis ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Wide Spectrum ◽  
Peripheral Circulation ◽  
Immunological Activity ◽  
Tissue Sections ◽  
Normal Appearing White Matter ◽  
Antigen Presenting

Multiple sclerosis (MS) has a wide spectrum of clinical courses, character ized by multifocal central nervous system (C NS) damage, postulated to be mediated by C NS antigen-specific T cells. Dendritic cells (DC), the most potent antigen-presenting cell, play a pivotal role in the decision between T-cell activation or anergy. Monoclonal antibodies to C D1a (immature DC) and C D83 (mature DC) were used to screen lesions with evidence of recent demyelinating activity and chronic plaque and normal appearing white matter (NAWM) tissue sections from 12 MS cases by immunocytochemistry. No C D1a-positive cells were detected in the MS or control C NS tissue blocks investigated. C D83-po sitive cells were not detected in tissues from any of the control cases or in the majority of perivascular cuffs in the MS tissue sections. However, in eight of the MS tissue blocks with evidence of recent demyelination, and in one block each from chronic plaque and NAWM, small numbers of distinct C D83-positive cells were present within occasional perivascular cuffs. In one area only of MS NAWM were C D83-po sitive cells detected in the tissue parenchyma, in an area of intense immunological activity. DC in MS tissue may originate in the peripheral circulation as monocytes or immature DC and migrate to areas of plaque in response to signals received from C NS-produced chemokines.

scholarly journals Mycobacterium tuberculosis infection induces il12rb1 splicing to generate a novel IL-12Rβ1 isoform that enhances DC migration

2010 ◽  
Vol 207 (3) ◽  
pp. 591-605 ◽  
Author(s):  
Richard T. Robinson ◽  
Shabaana A. Khader ◽  
Cynthia A. Martino ◽  
Jeffrey J. Fountain ◽  
Maria Teixeira-Coelho ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell Activation ◽  
Rna Splicing ◽  
Cell Activation ◽  
Transmembrane Domain ◽  
Tuberculosis Infection ◽  
Terminal Sequence ◽  
Mycobacterium Tuberculosis Infection

RNA splicing is an increasingly recognized regulator of immunity. Here, we demonstrate that after Mycobacterium tuberculosis infection (mRNA) il12rb1 is spliced by dendritic cells (DCs) to form an alternative (mRNA) il12rb1Δtm that encodes the protein IL-12Rβ1ΔTM. Compared with IL-12Rβ1, IL-12Rβ1ΔTM contains an altered C-terminal sequence and lacks a transmembrane domain. Expression of IL-12Rβ1ΔTM occurs in CD11c+ cells in the lungs during M. tuberculosis infection. Selective reconstitution of il12rb1−/− DCs with (mRNA) il12rb1 and/or (mRNA) il12rb1Δtm demonstrates that IL-12Rβ1ΔTM augments IL-12Rβ1-dependent DC migration and activation of M. tuberculosis-specific T cells. It cannot mediate these activities independently of IL12Rβ1. We hypothesize that M. tuberculosis-exposed DCs express IL-12Rβ1ΔTM to enhance IL-12Rβ1-dependent migration and promote M. tuberculosis–specific T cell activation. IL-12Rβ1ΔTM thus represents a novel positive-regulator of IL12Rβ1-dependent DC function and of the immune response to M. tuberculosis.

scholarly journals Human CD14hi monocytes and myeloid dendritic cells provide a cell contact–dependent costimulatory signal for early CD40 ligand expression

Blood ◽  
2011 ◽  
Vol 117 (5) ◽  
pp. 1585-1594 ◽  
Author(s):  
Sagarika Chakrabarty ◽  
James T. Snyder ◽  
Jijia Shen ◽  
Hooman Azmi ◽  
Paul Q. Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Myeloid Dendritic Cells ◽  
A Cell ◽  
Cd40l Expression ◽  
Antigen Presenting

Abstract CD40L on CD4+ T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4+ T cells is highly dependent on a cell-cell interaction with CD14hiCD16− monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14loCD16+ monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus–immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation.

scholarly journals Functional Ambivalence of Dendritic Cells: Tolerogenicity and Immunogenicity

2021 ◽  
Vol 22 (9) ◽  
pp. 4430
Author(s):  
Ji-Hee Nam ◽  
Jun-Ho Lee ◽  
So-Yeon Choi ◽  
Nam-Chul Jung ◽  
Jie-Young Song ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Inflammatory Diseases ◽  
Immunosuppressive Agents ◽  
Treg Cells ◽  
Peripheral Tolerance ◽  
Cell Mediated Immunity ◽  
Antigen Presenting

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and inducers of T cell-mediated immunity. Although DCs play a central role in promoting adaptive immune responses against growing tumors, they also establish and maintain peripheral tolerance. DC activity depends on the method of induction and/or the presence of immunosuppressive agents. Tolerogenic dendritic cells (tDCs) induce immune tolerance by activating CD4+CD25+Foxp3+ regulatory T (Treg) cells and/or by producing cytokines that inhibit T cell activation. These findings suggest that tDCs may be an effective treatment for autoimmune diseases, inflammatory diseases, and infertility.

scholarly journals Improved function and balance in T cell modulation by endothelial cells in young people

2021 ◽  
Author(s):  
Shu-Qian Tang ◽  
Wei-Li Yao ◽  
Yazhe Wang ◽  
Yuan-Yuan Zhang ◽  
Hong-Yan Zhao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Subset ◽  
Underlying Mechanism ◽  
T Cell Subsets ◽  
Effector T Cell ◽  
Improved Function ◽  
And Function

Elderly individuals exhibit unbalanced bone marrow (BM) effector T cell subset differentiation, such as increased T helper (Th)-1 and T cytotoxic (Tc)-1 cell frequencies, but the underlying mechanism still unclear. Endothelial cells (ECs) , which are instructive components of the BM microenvironment, exhibit the phenotype of semi-professional antigen-presenting cells and regulate T cell recruitment and activation. Thus, we compared the frequency and function of BM ECs, especially their capacity to regulate effector T cell subsets, between young and old healthy individuals, and explored the underlying mechanism of this immunomodulatory discrepancy. Although the young and old EC percentages were comparable, young ECs showed less reactive oxygen species and better migratory and tube-forming abilities than old ECs. Notably, young ECs regulated T cells to differentiate into fewer Th1 and Tc1 cells than old ECs. Reduced T cell activation molecules and inflammatory cytokines in young BM ECs may be the possible mechanism.

scholarly journals Non-Pathogenic Mopeia Virus Induces More Robust Activation of Plasmacytoid Dendritic Cells than Lassa Virus

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 287 ◽  
Author(s):  
Justine Schaeffer ◽  
Stéphanie Reynard ◽  
Xavier Carnec ◽  
Natalia Pietrosemoli ◽  
Marie-Agnès Dillies ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Plasmacytoid Dendritic Cells ◽  
Health Concern ◽  
Lassa Virus ◽  
Type I ◽  
Viral Haemorrhagic Fever

Lassa virus (LASV) causes a viral haemorrhagic fever in humans and is a major public health concern in West Africa. An efficient immune response to LASV appears to rely on type I interferon (IFN-I) production and T-cell activation. We evaluated the response of plasmacytoid dendritic cells (pDC) to LASV, as they are an important and early source of IFN-I. We compared the response of primary human pDCs to LASV and Mopeia virus (MOPV), which is very closely related to LASV, but non-pathogenic. We showed that pDCs are not productively infected by either MOPV or LASV, but produce IFN-I. However, the activation of pDCs was more robust in response to MOPV than LASV. In vivo, pDC activation may support the control of viral replication through IFN-I production, but also improve the induction of a global immune response. Therefore, pDC activation could play a role in the control of LASV infection.

Sign in / Sign up

Export Citation Format

Share Document