scholarly journals Inhalation of sulfur mustard causes long-term T cell-dependent inflammation: Possible role of Th17 cells in chronic lung pathology

2012 ◽  
Vol 13 (1) ◽  
pp. 101-108 ◽  
Author(s):  
Neerad C. Mishra ◽  
Jules Rir-sima-ah ◽  
Gary R. Grotendorst ◽  
Raymond J. Langley ◽  
Shashi P. Singh ◽  
...  
Keyword(s):  
T Cell ◽  
Th17 Cells ◽  
Sulfur Mustard ◽  
Lung Pathology

scholarly journals Comparative strategies to induce long-term graft acceptance in fully allogeneic renal versus cardiac allograft models by CD28-B7 T cell costimulatory blockade: role of thymus and spleen.

1998 ◽  
Vol 9 (5) ◽  
pp. 891-898
Author(s):  
M Schaub ◽  
T H Stadlbauer ◽  
A Chandraker ◽  
J P Vella ◽  
L A Turka ◽  
...  
Keyword(s):  
T Cell ◽  
Species Differences ◽  
Single Injection ◽  
Maintenance Phase ◽  
Cardiac Allograft ◽  
Costimulatory Blockade ◽  
Histocompatibility Complex ◽  
Donor Cells

Blocking CD28-B7 T cell costimulatory activation by the fusion protein CTLA4Ig prevents rejection and induces long-term graft acceptance in various experimental transplant models. There are reported differences in the efficacy of CTLA4Ig in renal and cardiac rodent allograft models, but it is not clear whether these are due to the strain or species differences investigated in the different studies reported. This study investigates the effect of blocking CD28-B7 T cell costimulation with murine CTLA4Ig in rat models of acute renal and cardiac allograft rejection models, using the same complete major histocompatibility complex-incompatible strain combination. A single injection of murine CTLA4Ig 2 d after engraftment was able to induce long-term graft acceptance (> 100 d) in 54% of Lewis rat recipients of Wistar-Furth kidneys. Transferring this protocol into the acute Wistar-Furth to Lewis heart allograft model resulted in a mean graft survival time of 24.7+/-16.9 d, and all grafts were ultimately rejected. Only concomitant injection of donor cells (4 x 10(7) splenocytes) plus a single injection of CTLA4Ig on the day of transplant could induce long-term graft acceptance in 50% of animals. In both the cardiac and renal transplant models, the thymus and spleen were required for induction of tolerance. The maintenance phase of tolerance, however, did not require an intact thymus but did require the presence of a spleen. These data have important clinical applicability because human studies with T cell costimulatory blockade are being planned.

scholarly journals HIV-specific T-cell Responses and Generalized Activation in HIV-1 Infected Long-term Non-progressors and Progressors from South India

2019 ◽  
Vol 16 (4) ◽  
pp. 302-314
Author(s):  
Chinnambedu Ravichandran Swathirajan ◽  
Ramachandran Vignesh ◽  
Greer Waldrop ◽  
Uma Shanmugasundaram ◽  
Pannerselvam Nandagopal ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Activation Rates ◽  
Hiv 1

Background:Anti-viral cytokine expressions by cytotoxic T-cells and lower activation rates have been reported to correlate with suppressed HIV replication in long-term non-progressors (LTNP). Immune mechanisms underlying disease non-progression in LTNP might vary with HIV-1 subtype and geographical locations.Objective:This study evaluates cytokine expression and T-cells activation in relation to disease non-progression in LTNP.Methods:HIV-1 Subtype C infected LTNP (n=20) and progressors (n=15) were enrolled and flowcytometry assays were performed to study HIV-specific CD8 T-cells expressing IL-2, IFN-γ, TNF-α and MIP-1β against gag and env peptides. CD4+ T-cell activation was evaluated by surface expression of HLADR and CD38.Results:Proportions of cytokines studied did not differ significantly between LTNP and progressors, while contrasting correlations with disease progression markers were observed in LTNP. CD4+ T-cell activation rates were significantly lower in LTNP compared to progressors which indicate the potential role of T-cell activation rates in disease non-progression in LTNP.Conclusion:LTNP and progressors showed similar CD8+ T-cell responses, but final conclusions can be drawn only by comparing multiple immune factors in larger LTNP cohort with HIV-1 infected individuals at various levels of disease progression. A possible role of HIV-1 subtype variation and ethnic differences in addition to host-genetic and viral factors cannot be ruled out.

T cell expansion study using the lesional skin provides evidence for the role of drug-specific Tc1 and Th17 cells in severe drug eruptions

2016 ◽  
Vol 84 (1) ◽  
pp. e7-e8
Author(s):  
Toshiharu Fujiyama ◽  
Hideo Hashizume ◽  
Takatsune Umayahara ◽  
Kazuki Tatsuno ◽  
Taisuke Ito ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Expansion ◽  
Th17 Cells ◽  
Lesional Skin ◽  
Drug Eruptions ◽  
T Cell Expansion

Calcium Signaling in T Cells and Chronic Inflammatory Disorders of the Oral Cavity

2021 ◽  
pp. 002203452199065
Author(s):  
S. Hasiakos ◽  
Y. Gwack ◽  
M. Kang ◽  
I. Nishimura
Keyword(s):  
T Cells ◽  
T Cell ◽  
Oral Cavity ◽  
Calcium Signaling ◽  
Signaling Pathways ◽  
Chronic Inflammation ◽  
Th17 Cells ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases

Acute immune responses to microbial insults in the oral cavity often progress to chronic inflammatory diseases such as periodontitis and apical periodontitis. Chronic oral inflammation causes destruction of the periodontium, potentially leading to loss of the dentition. Previous investigations have demonstrated that the composition of oral immune cells, rather than the overall extent of cellular infiltration, determines the pathological development of chronic inflammation. The role of T lymphocyte populations, including Th1, Th2, Th17, and Treg cells, has been extensively described. Studies now propose pathogenic Th17 cells as a distinct subset, uniquely classifiable from traditional Th17 populations. In situ differentiation of pathogenic Th17 cells has been verified as a source of destructive inflammation, which critically drives pathogenesis in chronic inflammatory diseases such as diabetes, rheumatoid arthritis, and inflammatory bowel disease. Pathogenic Th17 cells resemble a Th1 penotype and produce not only interleukin 17 (IL-17) but also γ-interferon (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The proinflammatory cytokine-specific mechanisms known to induce IL-17 expression in Th17 cells are well characterized; however, differentiation mechanisms that lead to pathogenic Th17 cells are less understood. Recently, Ca2+ signaling through Ca2+ release-activated Ca2+ channels (CRAC) in T cells has been uncovered as a major signaling axis involved in the regulation of T-cell-mediated chronic inflammation. In particular, pathogenic Th17 cell–mediated immunological diseases appear to be effectively targeted via such Ca2+ signaling pathways. Pathogenic plasticity of Th17 cells has been extensively illustrated in autoimmune and chronic inflammatory diseases. Although their specific causal relationship to oral infection-induced chronic inflammatory diseases is not fully established, pathogenic Th17 cells may be involved in the underlining mechanism. This review highlights the current understanding of T-cell phenotype regulation, calcium signaling pathways in this event, and the potential role of pathogenic Th17 cells in chronic inflammatory disorders of the oral cavity.

scholarly journals The role of synovial T-cell infiltration following knee joint injury in symptoms and progression to osteoarthritis

2019 ◽  
Author(s):  
Babak Moradi ◽  
Miriam T Jackson ◽  
Cindy C. Shu ◽  
Susan M Smith ◽  
Margaret M Smith ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Post Injury ◽  
Joint Injury ◽  
Cell Responses ◽  
Cellular Events ◽  
Bona Fide

AbstractObjectivesIdentification of osteoarthritis(OA)-specific synovial inflammatory pathways, and when in the clinical course they are active, is critical for their utility as therapeutic targets. We directly compared the mononuclear inflammatory/immune-cell responses following joint injury that does and does-not lead to OA, to define bona-fide OA-associated cellular events.MethodsWe undertook detailed temporal flow-cytometric and mRNA expression analysis in mice after sham or medial-meniscal-destiblization (DMM) surgery. We compared this with patients with meniscal injury and OA, and evaluated the role of synovial monocytes/macrophages versus lymphocytes in catabolic metalloproteinase secrection in vitro. We determined the effect of transient acute or delayed systemic T-cell depletion on DMM-induced OA pathology.ResultsOA-inducing/DMM and non-OA-inducing/Sham surgery had identical synovial monocyte/macrophage number, activation and polarization. The number and activation of synovial (not splenic or peripheral-blood) CD4 and CD8 lymphocytes was increased from 1-day after DMM versus Sham, and showed a persistent cyclical elevation throughout OA onset and progression. There was a temporal imbalance in synovial Th17/Treg and Th1/Th2 lymphocytes during DMM-induced OA initiation and progression. We confirmed early post-injury and late-OA CD3/CD8 T-cell responses in synovial tissues from patients, identified an association between CD8 and early post-injury symptoms, and defined a significant role for CD3+T-cells in synovial metalloproteinase secretion. Anti-CD3 cell-depletion studies in mice confirmed a key role for the earliest post-injury T-cell response in long-term OA pathology.ConclusionsWe identify a hitherto unappreciated pathophysiological role of acute T-cell activation after joint injury in long-term post-traumatic OA risk, providing a novel diagnostic and therapeutic target.Key MessagesWhat is already known about this subject?The presence of synovitis/joint-inflammation increases the risk not only of osteoarthritis (OA) progression but incident disease. While numerous inflammatory effectors including macrophages and lymphocytes have been identified in OA, their disease-specificity, temporal regulation, and association with risk of pathology onset and progression is lacking.How does this study add?By directly comparing the mononuclear inflammatory/immune-cell responses following significant joint injury that does (medial-meniscal-destabilization; DMM) and does-not (Sham-surgery) lead to OA in mice, we have defined bona-fide OA-associated cellular events. There was no difference in synovial or systemic monocyte/macrophage cell number, activation or polarization between DMM and Sham, both showing a successful wound-healing response. In contrast, increases in number and activation of synovial Th1- and Th17-CD4, and CD8 T-cells in DMM compared with Sham occurred within the first 3 days, and while recurring cyclically through subsequent disease onset, depletion studies indicated this initial influx was key to long-term ptOA risk.How might this impact on clinical practice of future developments?Acute increases in synovial T-cells following jont injury may be both a novel marker of OA risk, and a target to reduce long term structural damage.

scholarly journals Reference: The role of corticosteroids in a preterm infant with lung pathology in the first three months of life.

2021 ◽  
Author(s):  
Femi Adeniyi
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Scientific Evidence ◽  
Extensive Study ◽  
Preterm Neonates ◽  
Lung Pathology ◽  
Selective Treatment ◽  
Term Outcome ◽  
Long Term Outcome

Corticosteroids are helpful in the treatment of preterm neonates at risk of bronchopulmonary dysplasia (BPD). However, its usefulness depends on patient selection, the timing of intervention with a corticosteroid, and choice of corticosteroid. In making these clinical choices, one must consider both short and long-term outcomes. Although corticosteroid use has been available for decades in preterm neonatal care, many aspects of corticosteroid use are unresolved due to limited research. Corticosteroids cause upregulation of anti-inflammatory, inhibiting pro-inflammatory mediators at the genomic level. Furthermore, the benefits of using corticosteroids should outweigh the known risks. Here we will discuss the current literature to guide clinical practice—a literature search for evidence through the clinical database on EMBASE, Medline, PubMed, and Cochrane. The keywords are bronchopulmonary dysplasia, corticosteroids, and prematurity.Limitations.There is bias due to limited research available to provide a high level of scientific evidence on the use of different modes of administration, other agents compared to the systemic use of dexamethasone. Conclusion.The consensus in the prevention of BPD is selective treatment after one week of life with dexamethasone. There is limited evidence to suggest the role of prophylaxis hydrocortisone in preventing BPD and advise to be considered in centers with a high risk of BPD. An extensive study into prophylaxis hydrocortisone for prevention of BDP and long-term outcome appears to be promising.The role of instilled steroids with surfactants at birth appears promising in the single-center study. A multicentre double-blinded randomized intratracheal budesonide use at delivery will be valuable.

Abstract 65: T cell Differentiation in Human Kawasaki Disease and a Murine Model of Coronary Arteritis

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
I-Chun Lin ◽  
Hsuan-Chang Kuo ◽  
Ying-Jui Lin ◽  
Shao-Ju Chien ◽  
Chien-Fu Huang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Kawasaki Disease ◽  
Murine Model ◽  
Th17 Cells ◽  
T Cell Differentiation ◽  
Ivig Treatment ◽  
Th1 Cells ◽  
Coronary Arteritis

The role of T cell differentiation in the immunopathogenesis of Kawasaki disease (KD) remains unclear. The aim of this study is to elucidate the role of T cell subsets in coronary artery lesion (CAL) of KD. Peripheral blood was obtained in 10 patients with acute KD before and 1 week after intravenous gamma-immunoglobulin (IVIG) treatment and in 20 patients with past history of KD for more than 5~20 years. Meanwhile, induction of coronary arteritis was performed on wild type BALB/c mice by Lactobacillus casei cell wall extract (LCWE). Human peripheral blood leukocytes were analyzed by using flow cytometric analysis and murine hearts were examined for immunofluorescence study and for RNA expression levels. Results: Compared to the febrile controls, KD patients prior to IVIG treatment had increased percentage of CD3 + /CD4 + /interferon-γ + (T helper 1, Th1) cells and CD3 + /CD4 + /interleukin-17A + (Th17) cells (mean ± SD, 1.36% ± 1.39% and 0.51% ± 0.25%, respectively) among Th cells (CD3 + /CD4 + ). Both increases declined after IVIG treatment (0.71% ± 0.74% and 0.33% ± 0.18%) despite no statistically difference by Mann-Whitney test. None of these 10 acute KD patients developed CAL after IVIG treatment. However, patients with previous KD and definite CALs (n= 11) seemed to have higher percentage of Th17 cells (0.50% ± .025% versus 0.35% ± 0.23%) but similar level of Th1 cells (0.93% ± 0.51% versus 1.05% ± 0.64%) when compared to those without CAL (n= 9). Murine cardiac tissues displayed the presence of Th1 (double-stained with CD3 and T-bet) and Th17 cells (double-stained with CD3 and RORγt) during days 7 and 14 after LCWE treatment but not in PBS-treated mice. Compatible with these, cardiac mRNA levels showed both increased levels of IFN-γ and IL17A mRNA in LCWE-treated mice. Conclusions: Our initial data suggests that specific T cell differentiation into Th1 and Th17 cells occurred in both human KD and mice stimulated with LCWE. IVIG treatment was associated with the recovery of such T cell differentiation. However, the clinical application to predict IVIG responsiveness and future CAL development by such increase in the peripheral Th17 remains unclear. Further studies to elucidate the detailed immune regulation of these T subsets on CAL are warrant by using this LCWE murine model.

119 IL-6 is critical for memory responses elicited by Th17 cells to tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A130-A130
Author(s):  
Hannah Knochelmann ◽  
Connor Dwyer ◽  
Aubrey Smith ◽  
Megan Wyatt ◽  
Guillermo Rangel RIvera ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Ex Vivo ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Cell Product

BackgroundTranslation of novel T cell therapies is limited by cost and time-consuming protocols involving long-term T cell expansion. We found that shortening ex vivo expansion of either TCR-specific murine Th17 cells or human CAR Th17 cells licenses the cell product to eradicate large tumors in low doses and generate long-lived memory against tumor.1 Therapeutic Th17 cells induce the systemic release of IL-6, IL-17, GM-CSF, and MCP-1 among other cytokines in tumor-bearing hosts, reminiscent of clinical cytokine release syndrome. As the toxicity of cytokine release is managed in patients through IL-6 blockade, we addressed the impact of IL-6 on efficacy and durability of Th17 cell therapy. We hypothesized that IL-6, induced by Th17 cells, was fueling the durable memory properties of this cell product.MethodsTh17 cells were expanded ex vivo using the TRP-1 transgenic mouse model in which CD4+ T cells express a TCR that recognizes tyrosinase-related protein 1 on melanoma. Naïve CD4+ T cells were polarized to the Th17 phenotype and infused into mice with B16F10 melanoma after a nonmyeloablative total body irradiation (5 Gy) preparative regimen.ResultsIL-6 blockade, targeting either IL-6R or neutralization of the cytokine, did not significantly impact the primary immune response of adoptively transferred Th17 cells against tumor. However, administering IL-6 blockade acutely after Th17 transfer resulted in a higher incidence of tumor relapse upon secondary tumor challenge, thereby compromising long-lived antitumor immunity.1 Mounting a secondary response to tumor was dependent on CD4+ T cells, but not CD8+ T cells, persisting in the host. Mechanistically, IL-6 blockade reduced pSTAT3 and Bcl2 in transferred T cells but did not greatly impact the concentration of other systemic cytokines. As a small fraction of Tregs remain in the Th17 cell product ex vivo, we examined the engraftment of those Tregs after transfer. IL-6 was critical to suppress engraftment of FoxP3+ donor T cells from the CD4+ T cell product. Thus, IL-6 promoted robust tumor infiltration by donor effector over regulatory cells for early Th17 cells relative to cell products expanded longer durations ex vivo.1ConclusionsOverall, short-term expanded Th17 cells uniquely induced IL-6 unlike Th17 cells expanded longer ex vivo. IL-6 promoted Th17 survival, reduced engraftment of tumor-specific Tregs, and was critical to durable memory. This work may suggest that the universal strategy to inhibit IL-6 during cytokine release syndrome may come at the expense of long-term efficacy for specific cell therapy approaches.ReferenceKnochelmann HM, Dwyer CJ, Smith AS, Bowers JS, Wyatt MM, Nelson MH, Rangel Rivera GO, Horton JD, Krieg C, Armeson K, Lesinski GB, Rubinstein MP, Li Z, Paulos CM. IL-6 fuels durable memory for Th17 cell-mediated responses to tumors. Cancer Res. 2020. Epub ahead of print. PMID: 32561531.

scholarly journals The IgE production is initially induced in subcutaneous fat and depends on extrafollicular B cells

2021 ◽  
Author(s):  
Dmitrii Borisovich Chudakov ◽  
Gulnar Vaisovna Fattakhova ◽  
Mariya Vladimirovna Konovalova ◽  
Daria Sergeevna Tsaregorotseva ◽  
Marina Alexandrovna Shevchenko ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Fat Tissue ◽  
Class Switching ◽  
Regional Lymph Nodes

AbstractBackgroundGrowing body of evidence indicates that IgE production can be developed by mechanisms that differ from those responsible for IgG and IgA production. One potential possibility is generation of IgE producing cells from tissue-associated B-cells and/or through extrafollicular pathway. But the role of subcutaneous fat-associated B-cells in this process is poorly investigated. The aim of the present study was to investigate the role of different B- and T- cell subpopulations after long-term antigen administration in IgE response.MethodsBALB/c mice were immunized 3 times a eeks for 4 weeks in withers region enriched with subcutaneous fat with high and low antigen doses as well as by intraperitoneal route in region enriched with visceral fat for comparison.ResultsAfter long-term antigen administration that promotes the type of immune response which is more similar to one observed in young allergic children, subcutaneous fat tissue B-cells generates more rapid and active IgE class switched and IgE-produced cells. Although IgE production at later time points was initiated also in regional lymph nodes, the early IgE production was exclusively linked with subcutaneous fat. We observed that low-dose induced strong IgE production accompanied by minimal IgG1 production was linked with extrafollicular B-2 derived plasmablasts as well as extrafollicular T- helpers accumulation. Delayed IgE class switching in regional lymph nodes and visceral fat tissue was characterized by the absence of both stable plasmablasts and T-extrafollicular helpers accumulation.ConclusionExtrafollicular B- and T-cell responses in subcutaneous fat are necessary for early IgE class switching and sensitization process in the case of allergen penetration through skin.

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