The Immune Response to Autologous Bacteroides in Ankylosing Spondylitis Is Characterized by Reduced Interleukin 10 Production

2009 ◽  
Vol 36 (4) ◽  
pp. 797-800 ◽  
Author(s):  
SIMON M. STEBBINGS ◽  
CORINDA TAYLOR ◽  
GERALD W. TANNOCK ◽  
MARGARET A. BAIRD ◽  
JOHN HIGHTON
Keyword(s):  
Immune Response ◽  
Ankylosing Spondylitis ◽  
Mononuclear Cells ◽  
Intestinal Inflammation ◽  
Ex Vivo ◽  
Activity Index ◽  
Disease Activity Index ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Peripheral Blood Mononuclear

Objective.Ileocolitis is a recognized feature of ankylosing spondylitis (AS) and is likely to play a role in the pathogenesis of AS, in conjunction with the normal intestinal microbiota. In order to investigate the host immune response in AS, we measured cytokines in tissue culture following exposure of peripheral blood mononuclear cells (PBMC) to autologous colonic bacteria.Methods.Twenty-one patients with AS and 21 matched controls were recruited. Subjects in the AS group were assessed clinically.Bacteroidesspecies belonging to theB. fragilisgroup were selectively cultured from stool samples and paired with blood samples from each participant. Ten cultures of autologousBacteroideswere randomly selected from cultures grown from the fecal specimens of each of the 21 patients with AS and 21 controls. These were then tested for reactivity with PBMC and the cytokines produced by proliferating lymphocytes [interleukin 10 (IL-10), IL-17, interferon-γ, tumor necrosis factor-α] were measured in cell culture supernatants. Differences between groups were analyzed using censored normal regression analysis.Results.The patients with AS had severe active AS with Bath AS Disease Activity Index 5.5 (± 1.6) and C-reactive protein (mg/l) 13.8 (± 12.2) (mean ± standard deviation). IL-10 concentrations inex vivoassay supernatants were lower in the AS group compared with controls (p = 0.047). There were no statistically significant differences between the groups for other cytokines.Conclusion.In AS, reduced IL-10 production in response to stimulation with autologousBacteroidescultures may represent a mechanism by which intestinal inflammation develops and persists, a situation analogous to inflammatory bowel disease.

Multiple sclerosis-associated retroviral agent (MSRV)-stimulated cytokine production in patients with relapsing-remitting multiple sclerosis

2009 ◽  
Vol 15 (4) ◽  
pp. 443-447 ◽  
Author(s):  
M Saresella ◽  
A Rolland ◽  
I Marventano ◽  
R Cavarretta ◽  
D Caputo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Endogenous Retroviruses ◽  
Peripheral Blood Mononuclear ◽  
Human Endogenous Retroviruses ◽  
Relapsing Remitting ◽  
Factor Α ◽  
Relapsing Remitting Multiple Sclerosis

Background Human endogenous retroviruses are suggested to play a pathogenic role in multiple sclerosis (MS); one of such retroviruses, the MS-associated retroviral agent (MSRV) has repeatedly been isolated in MS patients. Objective and methods We analyzed cytokine profiles in MSRV envelope protein (MSRV ENV-SU)-stimulated peripheral blood mononuclear cells of 30 relapsing-remitting MS patients with either acute (AMS) ( n = 13) or stable (SMS) ( n = 17) disease. Results suggest that MSRV ENV-SU induces the production of inflammatory cytokines, including tumor necrosis factor-α ( P < 0.05) and interferon-γ ( P < 0.004) in AMS patients and of interleukin-10 ( P < 0.05), an inflammation-dampening cytokine, in SMS individuals. Conclusions These data strengthen the hypothesis indicating that MSRV could be involved in the pathogenesis of MS.

scholarly journals Blocking interferon γ reduces expression of chemokines CXCL9, CXCL10 and CXCL11 and decreases macrophage infiltration in ex vivo cultured arteries from patients with giant cell arteritis

2015 ◽  
Vol 75 (6) ◽  
pp. 1177-1186 ◽  
Author(s):  
Marc Corbera-Bellalta ◽  
Ester Planas-Rigol ◽  
Ester Lozano ◽  
Nekane Terrades-García ◽  
Marco A Alba ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Selective Reduction ◽  
Temporal Artery ◽  
Interferon Γ ◽  
Peripheral Blood Mononuclear ◽  
Temporal Arteries ◽  
Infiltrating Cells

BackgroundInterferon γ (IFNγ) is considered a seminal cytokine in the pathogenesis of giant cell arteritis (GCA), but its functional role has not been investigated. We explored changes in infiltrating cells and biomarkers elicited by blocking IFNγ with a neutralising monoclonal antibody, A6, in temporal arteries from patients with GCA.MethodsTemporal arteries from 34 patients with GCA (positive histology) and 21 controls were cultured on 3D matrix (Matrigel) and exposed to A6 or recombinant IFNγ. Changes in gene/protein expression were measured by qRT-PCR/western blot or immunoassay. Changes in infiltrating cells were assessed by immunohistochemistry/immunofluorescence. Chemotaxis/adhesion assays were performed with temporal artery-derived vascular smooth muscle cells (VSMCs) and peripheral blood mononuclear cells (PBMCs).ResultsBlocking endogenous IFNγ with A6 abrogated STAT-1 phosphorylation in cultured GCA arteries. Furthermore, selective reduction in CXCL9, CXCL10 and CXCL11 chemokine expression was observed along with reduction in infiltrating CD68 macrophages. Adding IFNγ elicited consistent opposite effects. IFNγ induced CXCL9, CXCL10, CXCL11, CCL2 and intracellular adhesion molecule-1 expression by cultured VSMC, resulting in increased PBMC chemotaxis/adhesion. Spontaneous expression of chemokines was higher in VSMC isolated from GCA-involved arteries than in those obtained from controls. Incubation of IFNγ-treated control arteries with PBMC resulted in adhesion/infiltration by CD68 macrophages, which did not occur in untreated arteries.ConclusionsOur ex vivo system suggests that IFNγ may play an important role in the recruitment of macrophages in GCA by inducing production of specific chemokines and adhesion molecules. Vascular wall components (ie, VSMC) are mediators of these functions and may facilitate progression of inflammatory infiltrates through the vessel wall.

scholarly journals Characterization of the IL-17 and CD4+ Th17 Cells in the Clinical Course of Dengue Virus Infections

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1435
Author(s):  
Luis Alberto Sánchez-Vargas ◽  
Karina Guadalupe Hernández-Flores ◽  
Pablo Thomas-Dupont ◽  
Irma Yadira Izaguirre-Hernández ◽  
Elvis Efraín Sánchez-Marce ◽  
...  
Keyword(s):  
Immune Response ◽  
Dengue Virus ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Hemorrhagic Fever ◽  
High Serum ◽  
World Health ◽  
Interleukin 17 ◽  
Peripheral Blood Mononuclear ◽  
Blood Samples

The aims of this study were to determine the involvement of interleukin 17 (IL-17) and IL-17-producing cells in dengue pathogenesis. Blood samples from dengue virus (DENV)-infected patients were collected on different days after the onset of symptoms. Patients were classified according to 1997 World Health Organization guidelines. Our study examined 152 blood samples from dengue fever (DF, n = 109) and dengue hemorrhagic fever (DHF, n = 43) patients and 90 blood samples from healthy controls (HC). High serum concentrations of IL-17A and IL-22 were also associated with DHF (IL-17A [DHF vs. DF, p < 0.01; DHF vs. HC, p < 0.0001]; IL-22 [DHF vs. DF, p < 0.05; DHF vs. HC, p < 0.0001]). Moreover, there was a positive correlation between serum levels of IL-17A and IL-23, a key cytokine that promotes IL-17-based immune responses (r = 0.4089, p < 0.0001). Consistent with the IL-17-biased immune response in DHF patients, we performed ex vivo activation of peripheral blood mononuclear cells (PBMCs) from DHF patients and flow cytometry analysis showed a robust IL-17-biased immune response, characterized by a high frequency of CD4+IL-17+ producing cells. Our results suggests IL-17-producing cells and their related cytokines can play a prominent role in this viral disease.

scholarly journals Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Qingqing Jiao ◽  
Cuiping Liu ◽  
Ziliang Yang ◽  
Qiang Ding ◽  
Miaomiao Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Disease Activity Index ◽  
Peripheral Tolerance ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Significant Difference

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.

scholarly journals Ex Vivo Generation of Donor Antigen-Specific Immunomodulatory Cells

2018 ◽  
Vol 27 (11) ◽  
pp. 1692-1704
Author(s):  
M. Watanabe ◽  
Makiko Kumagai-Braesch ◽  
M. Yao ◽  
S. Thunberg ◽  
D. Berglund ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Human Leukocyte ◽  
Interleukin 10 ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Foxp3 Mrna ◽  
Ifn Γ

Adoptive transfer of alloantigen-specific immunomodulatory cells generated ex vivo with anti-CD80/CD86 mAbs (2D10.4/IT2.2) holds promise for operational tolerance after transplantation. However, good manufacturing practice is required to allow widespread clinical application. Belatacept, a clinically approved cytotoxic T-lymphocyte antigen 4-immunoglobulin that also binds CD80/CD86, could be an alternative agent for 2D10.4/IT2.2. With the goal of generating an optimal cell treatment with clinically approved reagents, we evaluated the donor-specific immunomodulatory effects of belatacept- and 2D10.4/IT2.2-generated immunomodulatory cells. Immunomodulatory cells were generated by coculturing responder human peripheral blood mononuclear cells (PBMCs) (50 × 106 cells) with irradiated donor PBMCs (20 × 106 cells) from eight human leukocyte antigen-mismatched responder–donor pairs in the presence of either 2D10.4/IT2.2 (3 μg/106 cells) or belatacept (40 μg/106 cells). After 14 days of coculture, the frequencies of CD4+ T cells, CD8+ T cells, and natural killer cells as well as interferon gamma (IFN-γ) production in the 2D10.4/IT2.2- and belatacept-treated groups were lower than those in the control group. The percentage of CD19+ B cells was higher in the 2D10.4/IT2.2- and belatacept-treated groups than in the control group. The frequency of CD4+CD25+CD127lowFOXP3+ T cells increased from 4.1±1.0% (preculture) to 7.1±2.6% and 7.3±2.6% (day 14) in the 2D10.4/IT2.2- and belatacept-treated groups, respectively ( p<0.05). Concurrently, delta-2 FOXP3 mRNA expression increased significantly. Compared with cells derived from the no-antibody treated control group, cells generated from both the 2D10.4/IT2.2- and belatacept-treated groups produced lower IFN-γ and higher interleukin-10 levels in response to donor-antigens, as detected by enzyme-linked immunospot. Most importantly, 2D10.4/IT2.2- and belatacept-generated cells effectively impeded the proliferative responses of freshly isolated responder PBMCs against donor-antigens. Our results indicate that belatacept-generated donor-specific immunomodulatory cells possess comparable phenotypes and immunomodulatory efficacies to those generated with 2D10.4/IT2.2. We suggest that belatacept could be used for ex vivo generation of clinical grade alloantigen-specific immunomodulatory cells for tolerance induction after transplantation.

scholarly journals Designing a therapeutic SARS-CoV-2 T-cell-inducing vaccine for high-risk patient groups

2020 ◽  
Author(s):  
Hans-Georg Rammensee ◽  
Stefan Stevanović ◽  
Cécile Gouttefangeas ◽  
Sonja Heidu ◽  
Reinhild Klein ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Therapeutic Vaccine ◽  
High Risk Patient ◽  
Hla Class I ◽  
Interferon Γ ◽  
Peripheral Blood Mononuclear ◽  
Hla Class I Molecules ◽  
Hla Dr

Abstract Here, we describe the preliminary results of an experimental vaccination of a self-experimenting healthy volunteer with eight SARS-CoV-2-derived peptides: five predicted to bind to HLA class I molecules (CD8 peptides) and three predicted to bind to HLA-DR molecules (CD4 peptides). The vaccine formulation also included one long and one short CMV-pp65-derived peptide that had previously been administered to the same individual and could thus act as positive controls. It further contained the new adjuvant XS15 and was administered as an emulsion in Montanide as a single subcutaneous (s.c.) injection. Peripheral blood mononuclear cells (PBMCs) isolated from blood drawn on day 36 before vaccination and day 19 after vaccination were assessed using an ex vivo Interferon-γ ELISpot assay. We detected strong vaccine-induced T-cell responses against all four CD4 peptides and against the recall CMV CD8 epitope, but found no immune responses against the five predicted SARS-CoV-2 CD8 peptides. Antibody reactivity against all the SARS-CoV-2 CD4 peptides, as detected using ELISA, was negative or marginal. We interpret these results in terms of the prospects of a therapeutic vaccine to be applied in symptomatic COVID-19 patients. An advantage of this approach is the possibility to assess efficacy or failure within a short time after vaccination.

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