scholarly journals T Cell Vaccination Inhibits Th1/Th17/Tfh Frequencies and Production of Autoantibodies in Collagen-Induced Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Shan Li ◽  
Xiaoyin Niu ◽  
Yebin Xi ◽  
Shaohua Deng ◽  
Chengzhen Li ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Onset ◽  
Inflammatory Cells ◽  
Type Ii Collagen ◽  
Treated Group ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Cell Responses ◽  
T Cell Vaccination

The aim of this study is to determine whether the regulatory role of T cell vaccination (TCV) is through inhibition of Th1/Th17/Tfh and production of autoantibodies on collagen-induced arthritis (CIA). First, CIA mice were treated with TCV. After disease onset, the incidence and severity of change in joint histopathology were evaluated. Mice in the TCV-treated group showed less disease severity and less infiltration of inflammatory cells in the joint sections. TCV decreased the frequencies of Th1/Th17/Tfh cells and related cytokines. Reduction of IL-21 may be associated with both Tfh and Th17, which further influence B cell and T cell responses. In addition, inhibition of Th1/Th17/Tfh frequencies led to the reduced expression of T-bet, RORα, RORγt, and Bcl6. Lastly, the proliferation of type-II-collagen-(CII-) specific T cells and the production of anti-CII antibodies were inhibited in the TCV-treated group. The results provide novel evidence that the therapeutic effects of TCV on CIA are associated with the inhibition of Th1/Th17/Tfh frequencies and autoantibodies production.

scholarly journals Recombinant Galectin-1 and Its Genetic Delivery Suppress Collagen-Induced Arthritis via T Cell Apoptosis

1999 ◽  
Vol 190 (3) ◽  
pp. 385-398 ◽  
Author(s):  
Gabriel A. Rabinovich ◽  
Gordon Daly ◽  
Hanna Dreja ◽  
Hitakshi Tailor ◽  
Clelia M. Riera ◽  
...  
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Interleukin 2 ◽  
Disease Onset ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Gene Therapy Protocol ◽  
Lymph Node Cells

Galectin-1 (GAL-1), a member of a family of conserved β-galactoside–binding proteins, has been shown to induce in vitro apoptosis of activated T cells and immature thymocytes. We assessed the therapeutic effects and mechanisms of action of delivery of GAL-1 in a collagen-induced arthritis model. A single injection of syngeneic DBA/1 fibroblasts engineered to secrete GAL-1 at the day of disease onset was able to abrogate clinical and histopathological manifestations of arthritis. This effect was reproduced by daily administration of recombinant GAL-1. GAL-1 treatment resulted in reduction in anticollagen immunoglobulin (Ig)G levels. The cytokine profile in draining lymph node cells and the anticollagen IgG isotypes in mice sera at the end of the treatment clearly showed inhibition of the proinflammatory response and skewing towards a type 2–polarized immune reaction. Lymph node cells from mice engaged in the gene therapy protocol increased their susceptibility to antigen-induced apoptosis. Moreover, GAL-1–expressing fibroblasts and recombinant GAL-1 revealed a specific dose-dependent inhibitory effect in vitro in antigen-dependent interleukin 2 production to an Aq-restricted, collagen type 2–specific T cell hybridoma clone. Thus, a correlation between the apoptotic properties of GAL-1 in vitro and its immunomodulatory properties in vivo supports its therapeutic potential in the treatment of T helper cell type 1–mediated autoimmune disorders.

scholarly journals Mapping and role of T cell response in SARS-CoV-2–infected mice

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Zhen Zhuang ◽  
Xiaomin Lai ◽  
Jing Sun ◽  
Zhao Chen ◽  
Zhaoyong Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Target Cells ◽  
Type I ◽  
Cell Responses ◽  
T Cell Vaccination

Virus-specific T cells play essential roles in protection against multiple virus infections, including SARS-CoV and MERS-CoV. While SARS-CoV-2–specific T cells have been identified in COVID-19 patients, their role in the protection of SARS-CoV-2–infected mice is not established. Here, using mice sensitized for infection with SARS-CoV-2 by transduction with an adenovirus expressing the human receptor (Ad5-hACE2), we identified SARS-CoV-2–specific T cell epitopes recognized by CD4+ and CD8+ T cells in BALB/c and C57BL/6 mice. Virus-specific T cells were polyfunctional and were able to lyse target cells in vivo. Further, type I interferon pathway was proved to be critical for generating optimal antiviral T cell responses after SARS-CoV-2 infection. T cell vaccination alone partially protected SARS-CoV-2–infected mice from severe disease. In addition, the results demonstrated cross-reactive T cell responses between SARS-CoV and SARS-CoV-2, but not MERS-CoV, in mice. Understanding the role of the T cell response will guide immunopathogenesis studies of COVID-19 and vaccine design and validation.

scholarly journals T cell–specific STAT3 deficiency abrogates lupus nephritis

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1468-1472 ◽  
Author(s):  
N Yoshida ◽  
F He ◽  
V C Kyttaris
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Cell Responses ◽  
Cytokines And Chemokines ◽  
Novel Approach ◽  
Cell Tissue ◽  
External Stimuli

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.

scholarly journals Tolerogenic Splenic IDO+Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Jie Yang ◽  
Yiming Yang ◽  
Huahua Fan ◽  
Hejian Zou
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Foxp3 Expression ◽  
Treated Group ◽  
Treg Cells ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Collagen Induced Arthritis

TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs)in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c+DCs, termed “DCiTreg,” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activityin vitro. After reinfusion with DCiTreg, marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF-βproduction was high in the DCiTreg-treated group. DCiTregalso induced new iTregsin vivo. Moreover, the inhibitory activity of DCiTregon CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCsin vivo.

scholarly journals Depletion of alpha/beta T cells by a monoclonal antibody against the alpha/beta T cell receptor suppresses established adjuvant arthritis, but not established collagen-induced arthritis in rats.

1992 ◽  
Vol 175 (4) ◽  
pp. 907-915 ◽  
Author(s):  
S Yoshino ◽  
L G Cleland
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Adjuvant Arthritis ◽  
Inflammatory Cells ◽  
Cell Receptor ◽  
Collagen Induced Arthritis ◽  
Alpha Beta ◽  
Synovial Tissues

The effects of treatment with a monoclonal antibody (R73 mAb) against T cell receptor alpha/beta (TCR-alpha/beta) on both established adjuvant arthritis (EAA) and established collagen-induced arthritis (ECIA) in rats have been investigated. Rats were treated with R73 mAb when arthritis reached a peak. Treatment with the anti-TCR-alpha/beta mAb markedly suppressed EAA, whereas ECIA was not affected by the mAb treatment. Histologically, R73 mAb-treated rats with EAA showed mild hyperplasia of synovial tissues, sparse infiltration of inflammatory cells, and minimal erosion of cartilage, whereas arthritic rats treated with PBS and an irrelevant control mAb against Giardia had marked hyperplasia of synovium with pannus, massive inflammatory cell infiltrate, and severe destruction of cartilage and subchondral bone. R73 mAb-treated rats with ECIA exhibited pronounced formation of pannus containing many inflammatory cells and marked cartilage and subchondral damage similar to those in arthritic rats that received the control treatments. Treatment with R73 mAb depleted markedly alpha/beta+ T cells in both peripheral blood and synovial tissues of rats with EAA and ECIA. R73 mAb treatment was associated with marked reduction in arthritogen-specific delayed-type hypersensitivity responses in both EAA and ECIA. The titers of antibodies against type II collagen produced in rats with ECIA were not affected by the mAb. Thus, alpha/beta+ T cells appear to have a central role in EAA, but not in chronic ECIA.

scholarly journals Berberine Delays Onset of Collagen-Induced Arthritis through T Cell Suppression

2021 ◽  
Vol 22 (7) ◽  
pp. 3522
Author(s):  
Alexandra A. Vita ◽  
Hend Aljobaily ◽  
David O. Lyons ◽  
Nicholas A. Pullen
Keyword(s):  
T Cell ◽  
Type Ii Collagen ◽  
Control Group ◽  
Collagen Induced Arthritis ◽  
Preclinical Phase ◽  
T Cell Suppression ◽  
Cell Suppression ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

There is evidence that berberine (BBR), a clinically relevant plant compound, ameliorates clinically apparent collagen-induced arthritis (CIA) in vivo. However, to date, there are no studies involving the use of BBR which explore its prophylactic potential in this model of rheumatoid arthritis (RA). The aim of this study was to determine if prophylactic BBR use during the preclinical phase of collagen-induced arthritis would delay arthritic symptom onset, and to characterize the cellular mechanism underlying such an effect. DBA/1J mice were injected with an emulsion of bovine type II collagen (CII) and complete Freund’s adjuvant (day 0) and a booster injection of CII in incomplete Freund’s adjuvant (day 18) to induce arthritis. Mice were then given i.p. injections of 1 mg/kg/day of BBR or PBS (vehicle with 0.01% DMSO) from days 0 to 28, were left untreated (CIA control), or were in a non-arthritic control group (n = 15 per group). Incidence of arthritis in BBR-treated mice was 50%, compared to 90% in both the CIA and PBS controls. Populations of B and T cells from the spleens and draining lymph nodes of mice were examined on day 14 (n = 5 per group) and day 28 (n = 10 per group). BBR-treated mice had significantly reduced populations of CD4+Th and CD4+CXCR5+ Tfh cells, and an increased proportion of Foxp3+ Treg at days 14 and 28, as well as reduced expression of co-stimulatory molecules CD28 and CD154 at both endpoints. The effect seen on T cell populations and co-stimulatory molecule expression in BBR-treated mice was not mirrored in CD19+ B cells. Additionally, BBR-treated mice experienced reduced anti-CII IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement for RA, and that its effect may be mediated specifically through T cell suppression. However, the cellular effector involved raises concern for BBR prophylactic use in the context of vaccine efficacy and other primary adaptive immune responses.

scholarly journals Anti-C5a complementary peptide mitigates zymosan-induced severe peritonitis with fibrotic encapsulation in rats pretreated with methylglyoxal

2018 ◽  
Vol 315 (6) ◽  
pp. F1732-F1746 ◽  
Author(s):  
Daiki Iguchi ◽  
Masashi Mizuno ◽  
Yasuhiro Suzuki ◽  
Fumiko Sakata ◽  
Shoichi Maruyama ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Subsequent Development ◽  
Inflammatory Cells ◽  
Therapeutic Effects ◽  
Pathological Changes ◽  
Dialysis Patients ◽  
Visceral Peritoneum ◽  
Peritoneal Encapsulation ◽  
Severe Peritonitis

In a previous study of fungal peritoneal injury in peritoneal dialysis patients, complement (C)-dependent pathological changes were developed in zymosan (Zy)-induced peritonitis by peritoneal scraping. However, the injuries were limited to the parietal peritoneum and did not show any fibrous encapsulation of the visceral peritoneum, which differs from human encapsular peritoneal sclerosis (EPS). We investigated peritoneal injury in a rat model of Zy-induced peritonitis pretreated with methylglyoxal (MGO) instead of scraping (Zy/MGO peritonitis) to clarify the role of C in the process of fibrous encapsulation of the visceral peritoneum. Therapeutic effects of an anti-C5a complementary peptide, AcPepA, on peritonitis were also studied. In Zy/MGO peritonitis, peritoneal thickness, fibrin exudation, accumulation of inflammatory cells, and deposition of C3b and C5b-9 with loss of membrane C regulators were increased along the peritoneum until day 5. On day 14, fibrous encapsulation of the visceral peritoneum was observed, resembling human EPS. Peritoneal injuries and fibrous changes were significantly improved with AcPepA treatment, even when AcPepA was administered following injection of Zy in Zy/MGO peritonitis. The data show that C5a might play a role in the development of encapsulation-like changes in the visceral peritoneum in Zy/MGO peritonitis. AcPepA might have therapeutic effects in fungal infection-induced peritoneal injury by preventing subsequent development of peritoneal encapsulation.

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