scholarly journals Regulatory T cells: Therapeutic Potential for Treating Transplant Rejection and Type I Diabetes

10.3791/257 ◽  
2007 ◽  
Author(s):  
Jeffry A. Bluestone
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Therapeutic Potential ◽  
Type I Diabetes ◽  
Transplant Rejection ◽  
Type I

scholarly journals Tilting the Balance: Therapeutic Prospects of CD83 as a Checkpoint Molecule Controlling Resolution of Inflammation

2022 ◽  
Vol 23 (2) ◽  
pp. 732
Author(s):  
Katrin Peckert-Maier ◽  
Dmytro Royzman ◽  
Pia Langguth ◽  
Anita Marosan ◽  
Astrid Strack ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Transplant Rejection ◽  
Immune Checkpoints ◽  
Potential Candidate ◽  
Resolution Of Inflammation ◽  
Checkpoint Molecule

Chronic inflammatory diseases and transplant rejection represent major challenges for modern health care. Thus, identification of immune checkpoints that contribute to resolution of inflammation is key to developing novel therapeutic agents for those conditions. In recent years, the CD83 (cluster of differentiation 83) protein has emerged as an interesting potential candidate for such a “pro-resolution” therapy. This molecule occurs in a membrane-bound and a soluble isoform (mCD83 and sCD83, respectively), both of which are involved in resolution of inflammation. Originally described as a maturation marker on dendritic cells (DCs), mCD83 is also expressed by activated B and T cells as well as regulatory T cells (Tregs) and controls turnover of MHC II molecules in the thymus, and thereby positive selection of CD4+ T cells. Additionally, it serves to confine overshooting (auto-)immune responses. Consequently, animals with a conditional deletion of CD83 in DCs or regulatory T cells suffer from impaired resolution of inflammation. Pro-resolving effects of sCD83 became evident in pre-clinical autoimmune and transplantation models, where application of sCD83 reduced disease symptoms and enhanced allograft survival, respectively. Here, we summarize recent advances regarding CD83-mediated resolution of inflammatory responses, its binding partners as well as induced signaling pathways, and emphasize its therapeutic potential for future clinical trials.

scholarly journals Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility

2013 ◽  
Vol 43 (5) ◽  
pp. 1356-1362 ◽  
Author(s):  
Julie Tellier ◽  
Andry Andrianjaka ◽  
Rita Vicente ◽  
Nicolas Thiault ◽  
Geneviève Enault ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Type I Diabetes ◽  
Nod Mice ◽  
Type I ◽  
Diabetes Susceptibility ◽  
Thymic Development

scholarly journals The repertoire of newly developing regulatory T cells in the type I diabetes-prone NOD mouse is very diverse

Diabetes ◽  
2021 ◽  
pp. db201072
Author(s):  
Ariel Galindo-Albarrán ◽  
Sarah Castan ◽  
Jérémy C. Santamaria ◽  
Olivier P. Joffre ◽  
Bart Haegeman ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Type I Diabetes ◽  
Nod Mouse ◽  
Type I

scholarly journals Radon Therapy for Autoimmune Diseases Pemphigus and Diabetes: 2 Case Reports

Dose-Response ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 155932581985098 ◽  
Author(s):  
Shuji Kojima ◽  
Jerry M. Cuttler ◽  
Noriko Shimura ◽  
Hironobu Koga ◽  
Akihisa Murata ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Type I Diabetes ◽  
Case Reports ◽  
Type I ◽  
T Helper ◽  
T Helper 1 ◽  
Normal Ranges ◽  
Cell Balance

We report on the application of radon therapy to relieve the suffering of 2 patients with autoimmune diseases, one with pemphigus with an old myocardial infarction and diabetes mellitus and the other with type I diabetes. We include a lengthy discussion of the biological mechanisms that we believe produced the observed benefits. During the 6 to 9 months of the treatments, the marker values decreased to the upper limit of their normal ranges and the symptoms of the diseases were alleviated. Disorders of Th1/Th2 balance are implicated in the onset of many diseases, including autoimmune diseases. Our decision to give radon (222Rn) therapy to these patients was based on the results of 2 similar case reports and our earlier mouse experiments, which indicated that low doses of radiation induce regulatory T cells. Regulatory T cells regulate the T helper 1 cell and the T helper 2 cell balance. There are more than 80 different autoimmune diseases that are treated with anti-inflammatory agents or immune-suppressing drugs because the exact causes of these diseases and the cures are unknown. These and other case reports indicate that proper radon therapy is an effective treatment. We urge physicians to consider radon as a standard therapy for refractory autoimmune diseases.

scholarly journals MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jian Lu ◽  
Weiwei Wang ◽  
Peiyuan Li ◽  
Xiaodong Wang ◽  
Chao Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Transplant Rejection ◽  
Mouse Heart ◽  
Allograft Survival ◽  
Treg Function ◽  
Ifn Γ ◽  
Heart Transplant Rejection

AbstractRegulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4+ and CD8+ T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.

scholarly journals THU0051 LOW-DOSE INTERLEUKIN-2 SELECTIVELY EXPAND AND ACTIVATE REGULATORY T CELLS ACROSS 13 AUTOIMMUNE DISEASES.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 237.1-238
Author(s):  
M. Rosenzwajg ◽  
R. Lorenzon ◽  
P. Cacoub ◽  
F. Pitoiset ◽  
S. Aractingi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Inflammatory Disease ◽  
Low Dose ◽  
Therapeutic Potential ◽  
Interleukin 2 ◽  
Clinical Effects ◽  
Research Support ◽  
Open Label

Background:Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential for any autoimmune or inflammatory disease (AIID). We performed a disease-finding “basket trial” (TRANSREGNCT01988506) in patients affected by one of 11 different AIID and reported the outcome of the first 46 patients (Rosenzwajg et al, ARD 2019).Objectives:Here we analyzed and discussed results from deep immunophenotyping, of 78 patients, to comprehensively study the effect of ld-IL2 on the immune system of patients affected by various AIIDMethods:We performed a prospective, open label, phase I-IIa study in 78 patients with a mild to moderate form of one of 13 selected AIID. All patients received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Deep immunophenotyping was performed before and after 5 days of ld-IL2.Results:ld-IL2 significantly expands both memory Tregs as well as naïve Tregs, including recent thymic emigrant Tregs. It also activates Tregs as demonstrated by the significantly increased expression of HLA-DR, CD39, CD73, GITR, CTLA-4. Similar results were observed across the different AIID.Conclusion:ld-IL2 “universally” improves Treg fitness across 13 autoimmune and inflammatory disease.References:[1]Rosenzwajg M#, Lorenzon R#, Cacoub P, Pham HP, Pitoiset F, El Soufi K, RIbet C, Bernard C, Aractingi S, Banneville B, Beaugerie L, Berenbaum F, Champey J, Chazouilleres O, Corpechot C, Fautrel B, Mekinian A, Regnier E, Saadoun D, Salem JE, Sellam J, Seksik P, Daguenel-Nguyen A, Doppler V, Mariau J, Vicaut E, Klatzmann D. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019 Feb;78(2):209-217. doi: 10.1136/annrheumdis-2018-214229. Epub 2018 Nov 24.Disclosure of Interests:Michelle Rosenzwajg: None declared, Roberta Lorenzon: None declared, Patrice cacoub: None declared, Fabien Pitoiset: None declared, Selim Aractingi: None declared, Beatrice Banneville Speakers bureau: Lilly, Novartis, Laurent Beaugerie: None declared, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Julien Champey: None declared, Olivier Chazouilleres: None declared, Christophe Corpechot: None declared, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Arsene Mekinian: None declared, Elodie Regnier: None declared, david Saadoun: None declared, Joe-Elie Salem: None declared, Jérémie SELLAM: None declared, Philippe Seksik: None declared, David Klatzmann Consultant of: ILTOO Pharma

Phenotypic alterations, clinical impact and therapeutic potential of regulatory T cells in cancer

2014 ◽  
Vol 14 (7) ◽  
pp. 931-945 ◽  
Author(s):  
Belal Chaudhary ◽  
May Abd Al Samid ◽  
Basel K al-Ramadi ◽  
Eyad Elkord
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Therapeutic Potential ◽  
Clinical Impact

scholarly journals T cell receptor recognition of hybrid insulin peptides bound to HLA-DQ8

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mai T. Tran ◽  
Pouya Faridi ◽  
Jia Jia Lim ◽  
Yi Tian Ting ◽  
Goodluck Onwukwe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Type I Diabetes ◽  
Binding Motif ◽  
Type I ◽  
Cell Repertoire ◽  
Islet Amyloid ◽  
Autoreactive T Cell ◽  
Β Chain

AbstractHLA-DQ8, a genetic risk factor in type I diabetes (T1D), presents hybrid insulin peptides (HIPs) to autoreactive CD4+ T cells. The abundance of spliced peptides binding to HLA-DQ8 and how they are subsequently recognised by the autoreactive T cell repertoire is unknown. Here we report, the HIP (GQVELGGGNAVEVLK), derived from splicing of insulin and islet amyloid polypeptides, generates a preferred peptide-binding motif for HLA-DQ8. HLA-DQ8-HIP tetramer+ T cells from the peripheral blood of a T1D patient are characterised by repeated TRBV5 usage, which matches the TCR bias of CD4+ T cells reactive to the HIP peptide isolated from the pancreatic islets of a patient with T1D. The crystal structure of three TRBV5+ TCR-HLA-DQ8-HIP complexes shows that the TRBV5-encoded TCR β-chain forms a common landing pad on the HLA-DQ8 molecule. The N- and C-termini of the HIP is recognised predominantly by the TCR α-chain and TCR β-chain, respectively, in all three TCR ternary complexes. Accordingly, TRBV5 + TCR recognition of HIP peptides might occur via a ‘polarised’ mechanism, whereby each chain within the αβTCR heterodimer recognises distinct origins of the spliced peptide presented by HLA-DQ8.

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