scholarly journals Impact of Janus Kinase 3 on Cellular Ca2+ Release, Store Operated Ca2+ Entry and Na+/Ca2+ Exchanger Activity in Dendritic Cells

2015 ◽  
Vol 36 (6) ◽  
pp. 2287-2298 ◽  
Author(s):  
Jing Yan ◽  
Evi Schmid ◽  
Zohreh Hosseinzadeh ◽  
Sabina Honisch ◽  
Ekaterina Shumilina ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Function ◽  
Janus Kinase ◽  
Transient Increase ◽  
Electrogenic Transport ◽  
Cell Responses ◽  
Whole Cell Patch Clamp ◽  
Janus Kinase 3 ◽  
Antigen Presenting ◽  
Sustained Increase

Background/Aims: Janus kinase 3 (JAK3), a tyrosine kinase mainly expressed in hematopoietic cells, participates in the signaling stimulating cell proliferation. The kinase is expressed in dendritic cells (DCs), antigen presenting cells involved in the initiation and regulation of antigen-specific T-cell responses. Dendritic cell function is regulated by cytosolic Ca2+ activity ([Ca2+]i). Mediators increasing [Ca2+]i in DCs include ATP and the chemokine receptor CXCR4 ligand CXCL12. The present study explored, whether JAK3 participates in the regulation of [Ca2+]i in DCs. Methods: Fura-2 fluorescence was employed to determine [Ca2+]i, and whole cell patch clamp to decipher electrogenic transport in immature DCs isolated from bone marrow of JAK3-knockout (jak3-/-) or wild-type mice (jak3+/+). Results: Without treatment, [Ca2+]i was similar in jak3-/- and jak3+/+ DCs. Addition of ATP (100 µM) was followed by transient increase of [Ca2+]i reflecting Ca2+ release from intracellular stores, an effect significantly less pronounced in jak3-/- DCs than in jak3+/+ DCs. CXCL12 administration was followed by a sustained increase of [Ca2+]i reflecting receptor operated Ca2+ entry, an effect significantly less rapid in jak3-/- DCs than in jak3+/+ DCs. In addition, the Ca2+ release-activated Ca2+ channel (CRAC) current triggered by IP3-induced Ca2+ store depletion and CXCL12 was significantly higher in DCs from jak3+/+ mice than in jak3-/- mice. Inhibition of sarcoendoplasmatic reticulum Ca2+-ATPase (SERCA) by thapsigargin (1 µM) in the absence of extracellular Ca2+ was followed by a transient increase of [Ca2+]i reflecting Ca2+ release from intracellular stores, and subsequent readdition of extracellular Ca2+ in the continued presence of thapsigargin was followed by a sustained increase of [Ca2+]i reflecting store operated Ca2+ entry (SOCE). Both, Ca2+ release from intracellular stores and SOCE were again significantly lower in jak3-/- DCs than in jak3+/+ DCs. Pretreatment of jak3+/+ DCs with JAK inhibitor WHI-P154 (22 µM, 10 minutes or 24 hours) significantly blunted both thapsigargin induced Ca2+ release and subsequent SOCE. Abrupt replacement of Na+ containing (130 mM) and Ca2+ free (0 mM) extracellular bath by Na+ free (0 mM) and Ca2+ containing (2 mM) extracellular bath increased [Ca2+]i reflecting Na+/Ca2+ exchanger activity, an effect again significantly less pronounced in jak3-/- DCs than in jak3+/+ DCs. Conclusions: JAK3 deficiency is followed by down-regulation of cytosolic Ca2+ release, receptor and store operated Ca2+ entry and Na+/Ca2+ exchanger activity in DCs.

Antigen-presenting cell function of dendritic cells and macrophages in proliferative T cell responses to soluble and particulate antigens

1986 ◽  
Vol 16 (4) ◽  
pp. 345-350 ◽  
Author(s):  
Martien L. Kapsenberg ◽  
Marcel B. M. Teunissen ◽  
Frank E. M. Stiekema ◽  
Hiskias G. Keizer
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Function ◽  
T Cell Responses ◽  
Antigen Presenting Cell ◽  
Cell Responses ◽  
Antigen Presenting

Stimulation of autologous proliferative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2764-2771 ◽  
Author(s):  
Beth D. Harrison ◽  
Julie A. Adams ◽  
Mark Briggs ◽  
Michelle L. Brereton ◽  
John A. Liu Yin
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Dendritic Cells ◽  
T Cell ◽  
Myeloid Leukemia ◽  
T Cell Responses ◽  
Cell Responses ◽  
Antigen Presenting ◽  
Acute Myeloid ◽  
Stimulation Of

Abstract Effective presentation of tumor antigens is fundamental to strategies aimed at enrolling the immune system in eradication of residual disease after conventional treatments. Myeloid malignancies provide a unique opportunity to derive dendritic cells (DCs), functioning antigen-presenting cells, from the malignant cells themselves. These may then co-express leukemic antigens together with appropriate secondary signals and be used to generate a specific, antileukemic immune response. In this study, blasts from 40 patients with acute myeloid leukemia (AML) were cultured with combinations of granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor α, and development to DCs was assessed. After culture, cells from 24 samples exhibited morphological and immunophenotypic features of DCs, including expression of major histocompatibility complex class II, CD1a, CD83, and CD86, and were potent stimulators in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of autologous T-cell responses was assessed by the proliferative response of autologous T cells to the leukemic DCs and by demonstration of the induction of specific, autologous, antileukemic cytotoxicity. Of 17 samples, 11 were effective stimulators in the autologous MLR, and low, but consistent, autologous, antileukemic cytotoxicity was induced in 8 of 11 cases (mean, 27%; range, 17%-37%). This study indicates that cells with enhanced antigen-presenting ability can be generated from AML blasts, that these cells can effectively prime autologous cytotoxic T cells in vitro, and that they may be used as potential vaccines in the immunotherapy of AML.

scholarly journals CD40 in Clinical Inflammation: From Multiple Sclerosis to Atherosclerosis

1998 ◽  
Vol 6 (3-4) ◽  
pp. 215-222 ◽  
Author(s):  
Jon D. Laman ◽  
Mark De Boer ◽  
Bert A. 'T Hart
Keyword(s):  
Multiple Sclerosis ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cell ◽  
Antibody Production ◽  
Memory Formation ◽  
Isotype Switching ◽  
Cell Responses ◽  
Clinical Conditions ◽  
Antigen Presenting

The interactions of CD40 and CD40L have been known for some time to critically regulate B-cell responses with respect to proliferation, isotype switching, antibody production, and memory formation. More recent findings demonstrated that CD40 can be expressed on several other antigen-presenting cell (APC) types such as macrophages, dendritic cells, and fibroblasts. This expression of CD40 regulates T-cell-APC interaction and is centrally involved in a wide array of inflammatory events. Here, currently available data are reviewed demonstrating that CD40- CD40L interactions are operational in two chronic inflammatory clinical conditions, namely, multiple sclerosis and atherosclerosis. The functional correlates of these interactions are discussed in the light of recent other findings, shedding light on the multiple effects of CD40- CD40L interactions.

scholarly journals Induction of Polyomavirus-Specific CD8+T Lymphocytes by Distinct Dendritic Cell Subpopulations

2001 ◽  
Vol 75 (1) ◽  
pp. 544-547 ◽  
Author(s):  
Donald R. Drake ◽  
Mandy L. Shawver ◽  
Annette Hadley ◽  
Eric Butz ◽  
Charles Maliszewski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Epitope ◽  
T Cell Responses ◽  
T Cell Epitope ◽  
Cell Responses ◽  
Cd8 T Lymphocytes ◽  
Cell Subpopulations ◽  
Antigen Presenting

ABSTRACT Dendritic cells are pivotal antigen-presenting cells for generating adaptive T-cell responses. Here, we show that dendritic cells belonging to either the myeloid-related or lymphoid-related subset are permissive for infection by mouse polyomavirus and, when loaded with a peptide corresponding to the immunodominant anti-polyomavirus CD8+T-cell epitope or infected by polyomavirus, are each capable of driving expansion of primary polyomavirus-specific CD8+ T-cell responses in vivo.

scholarly journals Dendritic cells are potent antigen-presenting cells for microbial superantigens.

1992 ◽  
Vol 175 (1) ◽  
pp. 267-273 ◽  
Author(s):  
N Bhardwaj ◽  
S M Friedman ◽  
B C Cole ◽  
A J Nisanian
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Antigen Presenting Cells ◽  
Small Subset ◽  
Cell Functions ◽  
Cell Responses ◽  
Antigen Presenting

Dendritic cells are a small subset of human blood mononuclear cells that are potent stimulators of several T cell functions. Here we show they are 10-50-fold more potent than monocytes or B cells in inducing T cell responses to a panel of superantigens. Furthermore, dendritic cells can present femtomolar concentrations of superantigen to T cells even at numbers where other antigen-presenting cells (APCs) are inactive. Although dendritic cells express very high levels of the major histocompatibility complex products that are required to present superantigens, it is only necessary to pulse these APCs for 1 hour with picomolar levels of one superantigen, staphylococcal enterotoxin B, to maximally activate T cells. Our results suggest that very small amounts of superantigen will be immunogenic in vivo if presented on dendritic cells.

scholarly journals Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5152-5162 ◽  
Author(s):  
Adriano Boasso ◽  
Caroline M. Royle ◽  
Spyridon Doumazos ◽  
Veronica N. Aquino ◽  
Mara Biasin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Interaction ◽  
Type I ◽  
Cell Responses ◽  
Hiv Exposed ◽  
Antigen Presenting ◽  
Hiv Envelope

AbstractA delicate balance between immunostimulatory and immunosuppressive signals mediated by dendritic cells (DCs) and other antigen-presenting cells (APCs) regulates the strength and efficacy of antiviral T-cell responses. HIV is a potent activator of plasmacytoid DCs (pDCs), and chronic pDC activation by HIV promotes the pathogenesis of AIDS. Cholesterol is pivotal in maintaining HIV envelope integrity and allowing HIV-cell interaction. By depleting envelope-associated cholesterol to different degrees, we generated virions with reduced ability to activate pDCs. We found that APC activation was dissociated from the induction of type I IFN-α/β and indoleamine-2,3-dioxygenase (IDO)–mediated immunosuppression in vitro. Extensive cholesterol withdrawal, resulting in partial protein and RNA loss from the virions, rendered HIV a more powerful recall immunogen for stimulating memory CD8 T-cell responses in HIV-exposed, uninfected individuals. These enhanced responses were dependent on the inability of cholesterol-depleted HIV to induce IFN-α/β.

Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2258-2265 ◽  
Author(s):  
Marta Stanzani ◽  
Enrico Orciuolo ◽  
Russell Lewis ◽  
Dimitrios P. Kontoyiannis ◽  
Sergio L. R. Martins ◽  
...  
Keyword(s):  
T Cell ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Cell Function ◽  
T Cell Responses ◽  
Cell Responses ◽  
Cytokine Flow Cytometry ◽  
Induced Apoptosis ◽  
Antigen Presenting

AbstractAspergillus fumigatus (AF) is a ubiquitous mold and is the most common cause of invasive aspergillosis, an important source of morbidity and mortality in immunocompromised hosts. Using cytokine flow cytometry, we assessed the magnitude of functional CD4+ and CD8+ T-cell responses following stimulation with Aspergillus antigens. Relative to those seen with cytomegalovirus (CMV) or superantigen stimulation, responses to Aspergillus antigens were near background levels. Subsequently, we confirmed that gliotoxin, the most abundant mycotoxin produced by AF, was able to suppress functional T-cell responses following CMV or staphylococcal enterotoxin B (SEB) stimulation. Additional studies demonstrated that crude AF filtrates and purified gliotoxin inhibited antigen-presenting cell function and induced the preferential death of monocytes, leading to a marked decrease in the monocyte-lymphocyte ratio. Analysis of caspase-3 activation confirmed that gliotoxin preferentially induced apoptosis of monocytes; similar effects were observed in CD83+ monocyte-derived dendritic cells. Importantly, the physiologic effects of gliotoxin in vitro were observed below concentrations recently observed in the serum of patients with invasive aspergillosis. These studies suggest that the production of gliotoxin by AF may constitute an important immunoevasive mechanism that is mediated by direct effects on antigen-presenting cells and both direct and indirect effects on T cells.

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