Preoperative Low-Dose Irradiation Promotes Long-Term Allograft Acceptance and Induces Regulatory T Cells in a Porcine Model of Pulmonary Transplantation

2006 ◽  
Vol 82 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Gregor Warnecke ◽  
Murat Avsar ◽  
Manuel Morancho ◽  
Carsten Peters ◽  
Stefanie Thissen ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Low Dose ◽  
Porcine Model ◽  
Dose Irradiation

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

Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis

2021 ◽  
pp. 135245852110033
Author(s):  
Quentin Howlett-Prieto ◽  
Xuan Feng ◽  
John F Kramer ◽  
Kevin J Kramer ◽  
Timothy W Houston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
B Cell ◽  
Regulatory T Cell ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Long Term Treatment ◽  
Anti Cd20

Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients. Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry. Results: CD8+ CD28− regulatory cells rose from one-third of healthy control levels before ocrelizumab treatment (2.68% vs 7.98%), normalized by 12 months (13.5%), and rose to 2.4-fold above healthy controls after 18 months of ocrelizumab therapy (19.0%). CD4+ FOXP3+ regulatory cells were lower in MS than in healthy controls (7.98%) and showed slight long-term decreases with ocrelizumab. CD8+ CD28− and CD4+ FOXP3+ regulatory T cell percentages in IFN-β-treated MS patients were between those of untreated MS and healthy controls. Interpretation: Long-term treatment with ocrelizumab markedly enriches CD8+ CD28− regulatory T cells and corrects the low levels seen in MS before treatment, while slightly decreasing CD4+ FOXP3+ regulatory T cells. Homeostatic enrichment of regulatory CD8 T cells provides a mechanism, in addition to B cell depletion, for the benefits of anti-CD20 treatment in MS.

Low-dose of tacrolimus favors the induction of functional CD4+CD25+FoxP3+ regulatory T cells in solid-organ transplantation

2009 ◽  
Vol 9 (5) ◽  
pp. 564-569 ◽  
Author(s):  
Zhen Wang ◽  
Bingyi Shi ◽  
Hailong Jin ◽  
Li Xiao ◽  
Yongwei Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Organ Transplantation ◽  
Low Dose ◽  
Solid Organ Transplantation ◽  
Solid Organ

scholarly journals Low-dose IL-2 therapy limits the reduction in absolute numbers of circulating regulatory T cells in rheumatoid arthritis

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110113
Author(s):  
Sheng-Xiao Zhang ◽  
Jia Wang ◽  
Cai-Hong Wang ◽  
Rui-Huan Jia ◽  
Ming Yan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Side Effects ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Immune Tolerance ◽  
Low Dose ◽  
Fold Increase ◽  
Plain Language ◽  
T Subsets

Background: Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4+T subsets and the clinical feasibility of IL-2 therapies in patients with RA. Methods: The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment with 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment. Results: RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs ( p < 0.05). Patients treated with low-dose IL-2 had a three-fold increase in absolute anti-inflammatory Treg counts, as well as a two-fold increase in the other CD4+T subsets. Moreover, post-treatment levels of markers of disease activity in RA patients treated with IL-2 were significantly lower than the baseline values ( p < 0.001), with no apparent side effects. Conclusion: Decreased absolute counts of circulating CD4+T lymphocyte subsets were observed in patients with RA. Circulating Tregs, which mediate immune tolerance, may be involved in the pathogenesis and progression of RA; however, this was ameliorated by low-dose IL-2, without obvious side effects. Plain language summary Low-dose IL-2 treatment for rheumatoid arthritis • Circulating Tregs may be involved in the pathogenesis and progression of RA. • The absolute count of Tregs was significantly correlated with disease activity measures. • Low-dose IL-2 was able to effectively expade Tregs and help for RA patients’ symptoms remission without evaluated side effects.

Role of regulatory T cells in long-term immune dysfunction associated with severe sepsis

2010 ◽  
Vol 38 (8) ◽  
pp. 1718-1725 ◽  
Author(s):  
Daniele C. Nascimento ◽  
José C. Alves-Filho ◽  
Fabiane Sônego ◽  
Sandra Y. Fukada ◽  
Marcelo S. Pereira ◽  
...  
Keyword(s):  
T Cells ◽  
Severe Sepsis ◽  
Regulatory T Cells ◽  
Immune Dysfunction

scholarly journals Evidence That FoxP3+ Regulatory T Cells May Play a Role in Promoting Long-Term Acceptance of Composite Tissue Allotransplants

2011 ◽  
Vol 91 (8) ◽  
pp. 908-915 ◽  
Author(s):  
Larry D. Bozulic ◽  
Yujie Wen ◽  
Hong Xu ◽  
Suzanne T. Ildstad
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Composite Tissue

scholarly journals P04.34 Low-dose irradiation increases recruitment and effector function of tumor-specific T cells in experimental gliomas

2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii286-iii286
Author(s):  
X Zhang ◽  
K Sahm ◽  
J Sonner ◽  
K Jähne ◽  
M Breckwoldt ◽  
...  
Keyword(s):  
T Cells ◽  
Low Dose ◽  
Effector Function ◽  
Experimental Gliomas ◽  
Dose Irradiation

scholarly journals The numbers of peripheral regulatory T cells are reduced in patients with psoriatic arthritis and are restored by low-dose interleukin-2

2020 ◽  
Vol 11 ◽  
pp. 204062232091601 ◽  
Author(s):  
Jia Wang ◽  
Sheng-Xiao Zhang ◽  
Yu-Fei Hao ◽  
Meng-Ting Qiu ◽  
Jing Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Psoriatic Arthritis ◽  
Regulatory T Cells ◽  
Low Dose ◽  
Interleukin 2 ◽  
Health Assessment ◽  
Life Quality ◽  
T Cell Subsets ◽  
Physician Global Assessment ◽  
Disease Indicators

Background: Although regulatory T cells (Tregs) play crucial roles in the maintenance of immune hemostasis, the numbers of peripheral Tregs in patients with psoriatic arthritis (PsA) remain unclear. We measured these numbers and the efficacy and safety of low-dose interleukin-2 (IL-2) therapy. Methods: We recruited 95 PsA patients, of whom 22 received subcutaneous low-dose IL-2 [0.5 million international units (MIU) per day for 5 days] combined with conventional therapies. The absolute numbers of cells in peripheral CD4+ T cell subsets were measured via modified flow cytometry. Clinical and laboratory indicators were compared before and after treatment. Results: PsA patients had lower peripheral Treg numbers than healthy controls ( p < 0.01), correlating significantly and negatively with the levels of disease indicators ( p < 0.05). Although low-dose IL-2 significantly increased the Th17 and Treg numbers in PsA patients compared with the baseline values, the Treg numbers rose much more rapidly than those of Th17 cells, re-balancing the Th17 and Treg proportions. Low-dose IL-2 combination therapy rapidly reduced PsA disease activities as indicated by the DAS28 instrument, thus the number of tender joints, visual analog scale pain, physician global assessment, the dermatology life quality index score, and the health assessment questionnaire score (all p < 0.05). Conclusion: PsA patients exhibited low Treg numbers. Low-dose IL-2 combination treatment increased these numbers and relieved disease activity without any apparent side effects. Additional studies are required to explore the long-term immunoregulatory utility of IL-2 treatment.

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