scholarly journals The Supernatant of Tonsil-Derived Mesenchymal Stem Cell Has Antiallergic Effects in Allergic Rhinitis Mouse Model

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
In-Su Park ◽  
Ji Hye Kim ◽  
Jun-Sang Bae ◽  
Dong-Kyu Kim ◽  
Ji-Hun Mo
Keyword(s):  
Allergic Rhinitis ◽  
T Cell ◽  
Mouse Model ◽  
Map Kinase ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Treated Group ◽  
Receptor Signal ◽  
Significant Difference ◽  
The Impact

Background and Purpose. Recently, tonsil-derived mesenchymal stem cells (T-MSCs) have attracted great attention in various medical fields due to easier harvest of T-MSCs and more immunomodulatory effects than adipose-derived MSCs. However, there was still little evidence of the effect of conditioned media from T-MSCs (T-MSCs-CM) on allergic rhinitis (AR). Therefore, we investigated the impact of T-MSCs-CM on an AR mouse model. Methods. We isolated T-MSCs from human palatine tonsil and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM was evaluated in the AR mouse model that was randomly divided into five groups (negative control, positive control, and T-MSCs-CM treated (0.1 mg, 1 mg, and 10 mg)). To investigate the therapeutic effect, we analyzed rhinitis symptoms, serum immunoglobulin (Ig), inflammatory cells, and cytokine expression. We also assessed T cell receptor signal, including MAP kinase (ERK/JNK), p65, and NFAT1. Results. We identified the increment of TGF-β1, PGE2, and HGF in the T-MSCs-CM. In an animal study, the T-MSCs-CM-treated group showed significantly reduced allergic symptoms and infiltration of eosinophils and neutrophils in the nasal mucosa, whereas there was no significant difference in total IgE and the OVA-specific IgE level. Additionally, we found that the 10 mg T-MSCs-CM-treated group showed a significantly decreased IL-4 mRNA expression, compared to the (+) Con group. In the analysis of T cell receptor signal, the phosphorylation of MAP kinases, translocation of p65, and activation of NFAT1 were inhibited after T-MSCs-CM. Conclusions. Our findings suggest that T-MSCs-CM showed a partial immunomodulatory effect on the AR mouse model by the inhibition of T cell activation via MAP kinase, p65, and NFAT1.

An obligate role for T-cell receptor αβ+ T cells but not T-cell receptor γδ+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis

2001 ◽  
Vol 107 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Amy L. Woodward ◽  
Jonathan M. Spergel ◽  
Harri Alenius ◽  
Emiko Mizoguchi ◽  
Atul K. Bhan ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
B Cells ◽  
Mouse Model ◽  
T Cell Receptor ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Αβ T Cells

T-cell receptor pharmacodynamics associated with survival and response to tremelimumab (T) in combination with durvalumab (D) in patients (pts) with unresectable hepatocellular carcinoma (uHCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4087-4087
Author(s):  
Patricia McCoon ◽  
Young S Lee ◽  
Robin Kate Kelley ◽  
Violeta Beleva Guthrie ◽  
Song Wu ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Single Agent ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
Combination Regimen ◽  
Cell Counts ◽  
Significant Difference ◽  
Dose Dependent ◽  
Cell Clonal Expansion

4087 Background: Study 22, a phase 2 clinical study (NCT02519348) evaluating T (anti-CTLA-4) and D (anti-PD-L1) as monotherapies and in combination indicated the best efficacy-safety profile with a novel combination regimen containing a single, priming dose of T (T300+D). Additionally, an expansion of proliferative CD8+ lymphocytes at Day 15 was observed with T300+D that was associated with improved response. Here, an exploratory molecular analysis of peripheral blood T cell receptors is presented. Methods: Immune-checkpoint inhibitor-naïve pts were randomized to 1 of 2 T+D combinations: T300+D (T 300 mg [1 dose] + D 1500 mg, then D every 4 weeks [Q4W]) or T75+D (T 75 mg Q4W + D 1500 mg Q4W [4 doses], then D Q4W); or single agent D (1500 mg Q4W) or T (750 mg Q4W [7 doses] then Q12W). DNA was isolated from PAXgene-preserved whole blood collected at baseline and on Day 29 during the first cycle of Q4W dosing, and then underwent CDR3 sequencing of T-cell receptor β using the immunoSEQ Assay (Adaptive Biotechnologies, Seattle, WA). Associations with objective response rate (ORR) and overall survival (OS) were evaluated. Results: The number of evaluable pts, samples, and overall ORR and OS are provided (Table). Immunosequencing analysis did not reveal significant differences in baseline T-cell clonality across arms. Increased T-cell clonal expansion at Day 29 appeared to be T dose dependent (Table), with no significant difference in the median expansion between the D and T75+D arms. Across all arms, responders had a larger median number of expanded T-cell clones on Day 29 than nonresponders (77.5 vs 40), and this greater expansion trended with longer OS (Table). Further evaluation by arm demonstrated an increase in T-cell clonal expansion in responders vs nonresponders in the T300+D arm. Pts with T-cell expansion above the median in the T300+D and T75+D arms also exhibited longer OS. Both newly expanded and total expanded clones on Day 29 vs Day 1 were associated with improved OS. Conclusions: The observed T dose-dependent increase in T-cell clonal expansion trended with improved ORR and longer OS, with the greatest overall benefit seen with T300+D vs T75+D, D and T. This is consistent with the previously reported observation that T300+D led to the highest median proliferating CD8+ T-cell counts and radiographic response. Further work is needed to differentiate the relative contributions of CD4 and CD8 clonal expansion to increased efficacy. T300+D and D are being evaluated in the phase 3 HIMALAYA study (NCT03298451) in uHCC vs sorafenib. Funding: AstraZeneca. Clinical trial information: NCT02519348. [Table: see text]

scholarly journals Nr4a1 and Nr4a3 Reporter Mice Are Differentially Sensitive to T Cell Receptor Signal Strength and Duration

Cell Reports ◽  
2020 ◽  
Vol 33 (5) ◽  
pp. 108328
Author(s):  
Emma Jennings ◽  
Thomas A.E. Elliot ◽  
Natasha Thawait ◽  
Shivani Kanabar ◽  
Juan Carlos Yam-Puc ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Signal Strength ◽  
Cell Receptor ◽  
Reporter Mice ◽  
Receptor Signal

The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma

2010 ◽  
Vol 189 (4) ◽  
pp. i10-i10
Author(s):  
Konstanze Pechloff ◽  
Julian Holch ◽  
Uta Ferch ◽  
Marc Schweneker ◽  
Kristina Brunner ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Mouse Models ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Receptor Signal

scholarly journals A therapeutic anti-CD4 monoclonal antibody inhibits T cell receptor signal transduction in mouse autoimmune cardiomyopathy

2007 ◽  
Vol 120 (15) ◽  
pp. 1319-1325 ◽  
Author(s):  
Zhao-hui WANG ◽  
Yu-hua LIAO ◽  
Jing YUAN ◽  
Li ZHANG ◽  
Min WANG ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Monoclonal Antibody ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signal

scholarly journals Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire

2020 ◽  
Vol 11 ◽  
Author(s):  
Qing Liang ◽  
Meina Zhang ◽  
Yudi Hu ◽  
Wei Zhang ◽  
Ping Zhu ◽  
...  
Keyword(s):  
T Cell ◽  
Liver Fibrosis ◽  
T Cell Receptor ◽  
Stellate Cell ◽  
Cell Receptor ◽  
Rrna Gene ◽  
Immune Microenvironment ◽  
Immune Repertoire ◽  
Liver Fibrogenesis ◽  
The Impact

Gut microbiota (GM) modifies the intrahepatic immune microenvironment, but the underlying mechanisms remain poorly understood. Liver fibrosis-associated imprinting is predicted to be reflected in GM. This study investigated the link between GM and the intrahepatic T cell receptor (TCR) immune repertoire (IR), and whether GM modulates the intrahepatic immune microenvironment via TCR IR during liver fibrosis. We analyzed the correlation between GM and TCR IR during liver fibrogenesis. Accordingly, 16S rRNA gene sequencing (16S-seq) and bulk immune repertoire sequencing (IR-seq) were performed to characterize GM and intrahepatic TCR IR. Fecal microbial transplant (FMT) and TCRβ knockout (TcrbKO) mouse models were employed to determine the biological link between GM and TCR IR in liver fibrosis. We found that GM and intrahepatic TCR IR are highly correlated, with both showing reduced diversity and centralized distribution during liver fibrosis. The restoration of normal intestinal microbiota may reshape intrahepatic TCR IR and delay liver fibrosis. Interestingly, TCR IR ablation abrogated the impact of GM on liver fibrogenesis. Furthermore, GM modulated hepatic stellate cell (HSC) activation via TCR IR-mediated intrahepatic immune milieu. Our study demonstrates that GM, which exhibits cross-talk with the intrahepatic TCR IR, influences the intrahepatic immune microenvironment and liver fibrosis progression.

scholarly journals Phase separation of signaling molecules promotes T cell receptor signal transduction

Science ◽  
2016 ◽  
Vol 352 (6285) ◽  
pp. 595-599 ◽  
Author(s):  
Xiaolei Su ◽  
Jonathon A. Ditlev ◽  
Enfu Hui ◽  
Wenmin Xing ◽  
Sudeep Banjade ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Phase Separation ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Signaling Molecules ◽  
Receptor Signal

Acute Graft Versus Host Disease Reduces Human Thymic T Cell Differentiation without Acting on Thymocyte Proliferation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2184-2184
Author(s):  
Emmanuel Clave ◽  
Corinne Douay ◽  
Maryvonnick Carmagnat ◽  
Marc Busson ◽  
Regis Peffault de Latour ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Absolute Number ◽  
T Cell Differentiation ◽  
Graft Versus Host ◽  
Thymic Output ◽  
Thymocyte Proliferation ◽  
Significant Difference

Abstract Thymic function is essential for an efficient long term T cell reconstitution after Hematopoietic Stem cell Transplantation (HSCT). We and others have shown that several factors and especially Acute Graft Versus Host Disease (aGVHD) could have an important impact on thymic output as measured by “signal joint T cell Receptor Excision Circles” (sjTREC) quantification. In order to go further in the understanding of aGVHD action on thymic output we quantified the sjTREC (generated just before the T cell Receptor (TCR) alpha chain recombination) but also others TRECs generated during the TCR beta chain recombination, named betaTREC: sj/beta TREC ratio being a marker of thymocyte proliferation. A group of 13 aGVHD Patients was selected first because of a long term follow-up (> 24 months) and compared to a control group of 8 patients that did not have aGVHD, matched for age (mean 29.8 and 28.9 years for aGVHD and non aGVHD patients respectively). Patients received, mainly for leukemia (17 out 21), a Bone Marrow (14) or Peripheral Blood (7) HSCT from a sibling genoidentical donor. TRECs (sj and beta) were quantified by multiplex real-time PCR with albumin gene as standard, using genomic DNA extracted from peripheral blood mononuclear cell samples obtained before HSCT and at 3, 6, 12 and 24 months after. In parallel, absolute number of CD3+ and naïve T cells was measured by flow cytometry using antibodies against CD3, CD4, CD8, CD45RA and CD62L. In our patients, the percentage and absolute number of naïve T cells, as defined by the CD45RA+, CD62L+ phenotype, were not different between the 2 groups showing again the inability of this parameter to measure the recent thymic emigrants in HSCT. Mean sjTREC /150000 cells decreased in both categories of patient 3 months after HSCT. Then, for non aGVHD patients, they started to rise up to reach near normal level at 12 months but not for aGVHD patients where they keeped decreasing until 6 months. At this last time point mean aGVHD patient sjTREC/150000 cells was significantly lower than for non aGVHD patients (255 versus 2402 respectively, p=0.031, Mann-Whitney). This was still true for the mean absolute number of sjTREC (1.44 versus 27.33/mL of blood, p=0.007). Mean betaTREC /150000 cells showed no decrease for control patients but the same pattern than sjTREC for aGVHD patients with also a significant difference at 6 months (55 versus 2302 betaTREC /150000 cells for aGVHD and non aGVHD patients respectively, p=0.010). Finally, there was no significant difference between the 2 groups for the sj/beta ratio. These data confirm that aGVHD patients have a lower thymic output in the first months after HSCT. We also show that the decrease in the thymic output could not be explained by a reduced thymocyte proliferation since the sj/beta TREC ratio is not different between the 2 groups. It is better explained by a decrease in the number of thymocyte precursors that start to differentiate and recombine their TCR beta chain (as measured by beta TRECs). Altogether this suggests that during aGVHD, the allogeneic reaction on the recipient thymic cells could either impair the thymus seeding by the T cell precursors or provoke an inhibition of the signals that trigger the T cell differentiation.

Evolution of the Donor T Cell Repertoire In Allogeneic Stem Cell Transplant Recipients In the Second Decade After Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 831-831
Author(s):  
Robert Q. Le ◽  
J. Joseph Melenhorst ◽  
Brenna Hill ◽  
Sarfraz Memon ◽  
Minoo Battiwalla ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Cell Receptor ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Significant Difference

Abstract Abstract 831 After allogeneic stem cell transplantation (SCT), donor T lymphocyte immune function is slowly re-established in the recipient through reconstruction of the donor's post-thymic T cell repertoire and from T cell neogenesis in the thymus. Although long-term survivors from SCT appear healthy, their immune repertoire and differences from that of their donors have not been characterized. We studied 38 healthy patients surviving more than 10 years from a myeloablative SCT for hematological malignancy (median follow-up 12 years, range 10–16 years). T cell and natural killer (NK) cell repertoires in these patients were compared with cells from their stem cell donors cryopreserved at time of transplant and from the same donors at 10 year after SCT. The median age of both recipients and their sibling donors at time of transplant was identical (36 years). Patients received cyclosporine GVHD prophylaxis and delayed add-back of donor lymphocytes 30–90 days post transplant. Only one patient was on continued immunosuppressive treatment at the time of study. Compared with the donor pre-transplant counts there was no significant difference in the absolute lymphocyte, neutrophil, monocyte, CD4+ and CD8+ T cell, NK cell, and B cell subset counts. However, compared to their donors, recipients had a) significantly fewer naïve CD4+ and CD8+ T cells; b) lower T cell receptor excision circles levels; c) fewer CD4+ central memory T cells; d) more effector CD8+ T cells; e) and more FOXP3+ regulatory T cells. These data suggest that the patient had a persistent deficiency on T cell neogenesis. Molecular examination of the T cell receptor Vbeta (TCRBV) repertoire by spectratype analysis showed that there was no significant difference in total complexity score, defined as the sum of the number of discrete peaks for each Vbeta subfamily, between the patients and their donors. TCRBV subfamily spectratyping profiles of patients and donors, however, had diverged, with both gains and losses of peaks identifiable in both patient and donor. In conclusion, patients surviving 10 or more years after allogeneic SCT still show a T cell repertoire that reflects expansion of the donor-derived post thymic T cell compartment, with a limited contribution by new T cell generation and persistently increased Tregs. It therefore appears that a diverse TCRBV repertoire predominantly derived from the memory T cell pool is compatible with good health. Disclosures: No relevant conflicts of interest to declare.

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