Tumor Necrosis Factor-α Blockade Leads to Decreased Peripheral T Cell Reactivity and Increased Dendritic Cell Number in Peripheral Blood of Patients with Ankylosing Spondylitis

2008 ◽  
Vol 35 (11) ◽  
pp. 2220-2228 ◽  
Author(s):  
LIPING PANG ◽  
LISHA WANG ◽  
TALIN SUO ◽  
HUIQIN HAO ◽  
XIANFENG FANG ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Tumor Necrosis ◽  
T Cell Proliferation ◽  
Cell Reactivity ◽  
Etanercept Treatment ◽  
Tnf Α ◽  
T Cell Reactivity ◽  
Factor Α ◽  
Necrosis Factor

ObjectiveTo study the effect of tumor necrosis factor-α (TNF-α) antagonist (etanercept) treatment on the peripheral T cell reactivity of patients with ankylosing spondylitis (AS).MethodsPeripheral blood mononuclear cells were collected from 40 patients with AS at baseline, after 2 and 6 weeks of etanercept treatment or placebo treatment, and from healthy controls. The number of cells secreting various cytokines was detected by enzyme linked immunospot. Serum soluble interleukin 2 (IL-2) receptor level was measured by ELISA. T cell proliferation was assayed with the WST-1 live cell-staining method. The myeloid dendritic cell (mDC) and regulatory T cell (Treg) levels were analyzed by fluorescence activated cell sorting.ResultsAfter 2 and 6 weeks of etanercept treatment, the number of TNF-α-secreting monocytes decreased. Although the T cell proliferation rate remained stable, the number of T cells secreting IL-2 and interferon-γ under anti-CD3/anti-CD28 stimulation was significantly decreased. The level of serum soluble IL-2R (sIL-2R), a T cell activation marker, also declined. The changes in T cell reactivity were correlated with a significant increase in MHC Class II-positive mDC cells in circulation. An increase in Treg cell numbers was also observed.ConclusionThe anti-TNF-α therapy blockaded MHC Class II-positive mDC maturation, enhanced regulatory T cell levels, and suppressed the functions of effector T cells. The reduced T cell reactivity could contribute to the efficacy of the TNF-α antagonist therapy in patients with AS.

scholarly journals Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity

2001 ◽  
Vol 195 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Mauritius Menges ◽  
Susanne Rößner ◽  
Constanze Voigtländer ◽  
Heike Schindler ◽  
Nicole A. Kukutsch ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Immunity ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-α (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-α induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto-antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti-CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild-type led to the induction of peptide-specific predominantly interleukin (IL)-10–producing CD4+ T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF-α results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10–producing T cells in vivo and prevent EAE.

Eudesmin inhibits tumor necrosis factor-α production and T cell proliferation

1999 ◽  
Vol 22 (4) ◽  
pp. 348-353 ◽  
Author(s):  
Jae Youl Cho ◽  
Eun Sook Yoo ◽  
Kyoung Up Baik ◽  
Myung Hwan Park
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
T Cell Proliferation ◽  
Factor Α ◽  
Necrosis Factor

Relation of HLA-B27, Tumor Necrosis Factor-α Promoter Gene Polymorphisms, and T Cell Cytokine Production in Ankylosing Spondylitis — A Comprehensive Genotype-Phenotype Analysis from an Observational Cohort

2011 ◽  
Vol 38 (11) ◽  
pp. 2436-2441 ◽  
Author(s):  
DENIS A. PODDUBNYY ◽  
ELISABETH MÄRKER-HERMANN ◽  
WIEBKE KALUZA-SCHILLING ◽  
HENNING ZEIDLER ◽  
JURGEN BRAUN ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Hla B27 ◽  
Tnf Α ◽  
Promoter Gene ◽  
Clinical Measurements ◽  
Factor Α ◽  
Necrosis Factor ◽  
Cell Cytokine Production

Objective.In a pilot study, a distinct T cell cytokine pattern associated with HLA-B27 status and a tumor necrosis factor-α (TNF-α) promoter gene polymorphism was found at –308 (TNF–308). The objective of our study was to assess these associations in a different cohort of patients with ankylosing spondylitis (AS) and to evaluate any effect on clinical measurements.Methods.Peripheral T cell cytokine production of patients with AS (n = 121) from the German Spondyloarthritis Inception Cohort was assessed by flow cytometry and correlated with HLA-B27, TNF–238, and TNF–308, and with clinical measurements.Results.In HLA-B27-positive, anti-TNF-naive patients with AS, the percentages of TNF-α-producing (5.02%) and interleukin 10-producing (0.31%) CD8+ cells were significantly lower in comparison to HLA-B27-negative patients (9.52%, p = 0.048, and 0.46%, p = 0.037, respectively). A nonsignificant trend was found for a lower production of TNF-α by CD4+ and interferon-γ by both CD4+ and CD8+ T cells, as compared to HLA-B27-negative patients with AS (p > 0.05 for all comparisons). The A allele at TNF–308 was associated with a lower percentage of TNF-α-producing CD4+ T cells. No significant correlations were found between clinical or radiological measurements and cytokine production or with TNF-α promoter gene polymorphisms.Conclusion.Modulation of T cell cytokines by HLA-B27 might play a role in AS pathogenesis in B27-positive individuals. No conclusive data were obtained for the TNF–308 polymorphism on cytokine production, and no effect of cytokines or genetic polymorphisms on clinical manifestations was observed.

scholarly journals Spontaneous Development of Psoriasis in a New Animal Model Shows an Essential Role for Resident T Cells and Tumor Necrosis Factor-α

2004 ◽  
Vol 199 (5) ◽  
pp. 731-736 ◽  
Author(s):  
Onur Boyman ◽  
Hans Peter Hefti ◽  
Curdin Conrad ◽  
Brian J. Nickoloff ◽  
Mark Suter ◽  
...  
Keyword(s):  
Animal Model ◽  
T Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Skin Lesions ◽  
T Cell Proliferation ◽  
Factor Α ◽  
Necrosis Factor

Psoriasis is a common T cell–mediated autoimmune disorder where primary onset of skin lesions is followed by chronic relapses. Progress in defining the mechanism for initiation of pathological events has been hampered by the lack of a relevant experimental model in which psoriasis develops spontaneously. We present a new animal model in which skin lesions spontaneously developed when symptomless prepsoriatic human skin was engrafted onto AGR129 mice, deficient in type I and type II interferon receptors and for the recombination activating gene 2. Upon engraftment, resident human T cells in prepsoriatic skin underwent local proliferation. T cell proliferation was crucial for development of a psoriatic phenotype because blocking of T cells led to inhibition of psoriasis development. Tumor necrosis factor-α was a key regulator of local T cell proliferation and subsequent disease development. Our observations highlight the importance of resident T cells in the context of lesional tumor necrosis factor-α production during development of a psoriatic lesion. These findings underline the importance of resident immune cells in psoriasis and will have implications for new therapeutic strategies for psoriasis and other T cell–mediated diseases.

Dendritic Cells Co-Developing from Human CD34+ Cells Following Incubation with Thrombopoietin and Tumor Necrosis Factor-α Phagocytose Self-Megakaryocytic Progenitors and Induce Autologous T-Cell Proliferation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4132-4132
Author(s):  
Kunie Saito ◽  
Makoto Hirokawa ◽  
Hiroshi Fukaya ◽  
Yoshinari Kawabata ◽  
AtAtsushi Komatsuda ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
T Cell Proliferation ◽  
Megakaryocytic Differentiation ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background. Thrombopoietin (TPO) and tumor necrosis factor-α (TNF-α) sustain differentiation and proliferation of CD34+ cells toward dendritic cells (DC) in the presence of multi-acting cytokines. Therefore, we hypothesized that stimulation of human CD34+ cells with TPO and TNF-α might co-develop megakaryocytic progenitors and DC, which may relate to the induction of immune tolerance and autoimmunity in megakaryopoiesis. Materials and Methods. Highly purified human CD34+ cells were cultured in liquid phase with TPO, with or without TNF-α, and induced to undergo megakaryocytic differentiation. We enumerated megakaryocytic progenitor cells using the specific markers CD41, CD42b and CD61, and DC using CD4, CD11c, CD80, CD83, CD86 and CD123. The character and roles of co-developing non-megakaryocytic cells in the presence of TNF-α were analyzed using fluorescent activating cell sorter, enzyme immunohistochemistry, confocal microscopy and autologous mixed lymphocyte reaction (AMLR). Results. When CD34+ cells were cultured for 7 days in the presence of TPO at 100 ng/ml, the generated cells predominantly expressed CD41 (95±2%), CD42b (54±12%) and CD61 (96±2%), while rarely expressed CD11c (1.6±1.3%), CD80 (0.1±0.1%), CD83 (0.8±0.6%) or CD86 (3.3±1.9%). In contrast, addition of TNF-α at 100 ng/ml significantly decreased cells expressing CD41 (3.0±0.6%), CD42b (3.3±1.0%) or CD61 (3.2±0.9%), but did not affect the number of total cells. In the presence of TNF-α, the generated cells expressed HLA class I (100%) and HLA class II (100%), and a substantial number of cells became positive for CD11c (37±1%), even costimulatory molecules, such as CD80 (2.4±1.9%), D83 (8±4%) and CD86 (18±7%). TNF-α induced apoptosis of megakaryocytic cells. Immature CD11c+ DC was physically associated with apoptotic and CD61+ cells and was capable of endocytosing CD61+ cells. All of CD11c+ cells co-expressed c-mpl, CD4 and CD123, and about a half of CD11c+ cells co-expressed CD86. Cells generated by TNF-α and TPO (DC: TPO+TNF-α) induced autologous T cell proliferation in AMLR assay, however, cells generated by TNF-α alone (DC: TNF-α) did not (Figure 1A). Immunophenotypic analysis of both populations showed the higher expression of co-stimulatory molecules such as CD80, CD83 and CD86 in cells generated by TNF-α and TPO (Figure 1B). Conclusions. Non-megakaryocytic cells co-generated from human CD34+ cells during megakaryocytic differentiation in the presence of TPO and TNF-α express DC phenotypes. The CD4+/CD11c+/CD123+ DC subset physically and selectively associates with developing immature megakaryocytic cells and then obtains and captures self-substances and are functional in AMLR. These findings suggest that DC generated from human CD34+ cells under megakaryocytic and inflammatory co-stimuli obtain a functional role and possibly leading to the antigen presentation to induce immunity or tolerance against megakaryocytic cells and/or platelets. Figure Figure

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor
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