scholarly journals AB1068 REGULATORY EFFECT OF SHORT-TERM LOW DOSE OF IL-2 RESTORES REGULATORY T CELLS IN IgG4-RELATED DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1823.2-1823
Author(s):  
Y. Wu ◽  
X. C. Zhao ◽  
J. Luo
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Low Dose ◽  
Immune Cell ◽  
Interleukin 2 ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
The Absolute

Background:Little known about the roles of peripheral immune cell subsets in IgG4-related disease (IgG4-RD).Objectives:The aim of our study was to analyze the role of low-dose interleukin-2 (ld-IL2) on these cells in IgG4-RD.Methods:The percentage and absolute counts of lymphocyte subpopulations [CD3+ (T cells), CD4+, CD8+, CD19+ (B cells) and CD16+CD56+ (NK cells)] and CD4+T cell subsets (Th1, Th2, Th17, regulatory T (Treg)) using single platform flow cytometry in 25 IgG4-RD patients which were admitted and treated, as well as 24 healthy controls (HCs). Among IgG4-RD patients, 19 patients given only conventional treatments while 5 patients were were not only given conventional treatments but also received ld-IL2 (0.5 million IU/day) for 5 days.Results:We found that the absolute counts of T, CD4+T and Th1 cells were increased in the peripheral immune cells of IgG4-RD patients when compared with HCs. Meanwhile, the percentage of B, Th2, Th17 and Treg cells demonstrated significantly decreased. The ratio of Th1/Th2 and Th1/Treg in IgG4-RD patients were higher than that in HCs. After IL-2 administration, the absolute numbers of Treg cells increased dramatically, furthermore, the proportion of Treg cells had a trend towards higher values compared with those before treatment. Conversely, the ratio of Th2/Treg was downward. There were no any significant differences in the above subsets between before and after conventional treatments.Conclusion:Our findings support that the reduction of Treg cells in IgG4-RD patients, as well as ld-IL2 combined with conventional treatments were able to restore the Treg cells.References:[1]Akiyama M, Sasaki T, Kaneko Y, et al. Serum soluble interleukin-2 receptor is a useful biomarker for disease activity but not for differential diagnosis in IgG4-related disease and primary Sjögren’s syndrome adults from a defined population. Clin Exp Rheumatol, 2018.[2]Zhang SX, Wang J, Sun HH et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis, 2019.Disclosure of Interests:None declared

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.

Effects of Daily Low Dose IL-2 Therapy on Homeostatic Regulation of CD4+Foxp3+ Regulatory T Cells In Patients with Chronic Graft-Versus-Host Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 895-895
Author(s):  
Ken-ichi Matsuoka ◽  
John Koreth ◽  
Haesook T. Kim ◽  
O. Gregory Bascug ◽  
Sean McDonough ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Low Dose ◽  
Interleukin 2 ◽  
Absolute Number ◽  
Dependent Manner ◽  
Ki 67 ◽  
Hematopoietic Stem ◽  
Baseline Levels ◽  
The Absolute

Abstract Abstract 895 CD4+FoxP3+ regulatory T cells (Treg) play a central role in the maintenance of tolerance after allogeneic hematopoietic stem cell transplantation (HSCT) and recent studies have demonstrated that Treg deficiency leads to the development of chronic GHVD (cGVHD). Interleukin-2 (IL-2) is known to promote thymic generation and maintenance of peripheral Treg and IL-2 deficiency results in a profound deficiency of Treg in vivo. Based on these findings we initiated a clinical trial to evaluate the safety, clinical efficacy and immunologic effects of low dose recombinant IL-2 in patients with steroid-refractory cGVHD. We recently reported the clinical outcomes of this trial demonstrating that IL-2 administration preferentially increased Treg in patients with active cGVHD and resulted in clinical improvement with only minor toxicities (Koreth et al, ASBMT 2010). However, the mechanisms responsible for Treg expansion in patients during IL-2 administration have not been characterized. To elucidate these mechanisms, we examined phenotypic and functional characteristics of Treg in 14 patients who received daily subcutaneous IL-2 (3×105-3×106IU/m2/day) for 8 weeks. Peripheral blood samples were obtained before and at 1, 2, 4, 6, 8, 10 and 12 weeks after starting IL-2. Treg were compared to conventional CD4+FoxP3- T cells (Tcon) within individual patient samples and examined for expression of Ki-67, PD-1 and BCL-2. In some experiments, Treg and Tcon were further divided into subpopulations by the expression of CD45RA and CD31. Absolute numbers of functionally suppressive Treg increased 5-fold in the first 4 weeks of therapy. Treg numbers then slowly decreased despite continued IL-2 therapy, but remained 2-fold higher than baseline at 8 weeks. Absolute numbers of Tcon increased 2-fold in the first 4 weeks and then returned to baseline levels at 8 weeks. This resulted in a sustained increase of Treg/Tcon ratio for the entire duration of therapy, which persisted for at least 4 weeks after treatment was completed. Plasma IL-2 levels peaked at 1 week and gradually declined despite continued treatment at the same dose. Nevertheless, IL-2 levels remained significantly higher than baseline throughout treatment (median 1.4pg/ml at baseline and 18.1pg/ml at 8 weeks, p<0.05). The proliferative response to IL-2 was examined by measuring expression of Ki-67 in each subset. Initially, Ki-67 expression in Treg rapidly increased in an IL-2 dose-dependent manner. Ki-67 also increased in Tcon but at a significantly lower level (median 20.0% Treg vs 6.7% Tcon, p=0.0001). Increased Ki-67 was seen in both CD45RA+CD31+ recent thymic emigrant Treg (RTE-Treg) and CD45RA- activated/memory Treg (MEM-Treg) at similar levels (median 20.1% and 18.5%, respectively, p=0.54). Treg proliferation peaked in the first week of IL-2, and rapidly returned to baseline levels in weeks 2–3. Despite changes in proliferation, the absolute number of RTE-Treg remained significantly elevated (median 1.05/ul at baseline, 9.43/ul at 4 weeks, p=0.001). In contrast, the absolute number of RTE-Tcon did not change. Phenotypic analysis of Treg showed that expression of both PD-1 and BCL-2 increased during IL-2 therapy (%PD-1+ Treg; median 15.7% at baseline and 38.3% at 8 weeks, p=0.02: relative BCL-2 MFI; median 1.00 at baseline and 1.59 at 8 weeks, p=0.04). To determine the functional effects of these changes on susceptibility to apoptosis, Treg and Tcon were purified and cultured with or without agonistic FAS antibody, and apoptosis was measured using Annexin-V staining. Remarkably, Treg obtained during IL-2 therapy were relatively resistant to apoptosis compared to baseline. In summary, these results indicate that the selective expansion of Treg during prolonged IL-2 administration is characterized by a series of homeostatic changes. Initial high levels of IL-2 lead to selective and rapid Treg proliferation. Treg proliferation is not maintained as numbers of Treg increase and IL-2 levels decrease. Subsequent maintenance of increased Treg appears to be mediated primarily by increased resistance to apoptosis and prolonged survival. Increased thymic output of Treg also appears to support this peripheral homeostatic process. These findings demonstrate the complex effects of IL-2 on Treg homeostasis and provide important information for developing strategies to promote immune tolerance. Disclosures: No relevant conflicts of interest to declare.

scholarly journals AB0588 INFECTION AGGRAVATED DECREASE OF THE LEVEL OF TH17 AND TREG CELLS AND LOW-DOSE IL-2 REBALANCED TH17/TREG IN THE PERIPHERAL BLOOD OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1591.3-1591
Author(s):  
Y. Liang ◽  
H. Y. Wen ◽  
Y. Duan ◽  
Y. Liu ◽  
Z. Yu ◽  
...  
Keyword(s):  
T Cells ◽  
Low Dose ◽  
Lymphocyte Subsets ◽  
Absolute Number ◽  
Treg Cells ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Infection Group ◽  
The Absolute ◽  
Organ Infection

Background:Idiopathic inflammatory myopathies (IIM) are featured by a series of clinical presentation such as proximal muscle weakness, increased serum levels of creatine kinase and other muscle enzymes and involvement of other organs and systems[1, 2], which results in high morbidity and early mortality[3]. We have known the changes of the level of Th17 and Treg cells in IIM in previous studies[4-6]. However, whether infection affects lymphocyte subsets or not and whether the effect of low-dose interleukin-2 (IL-2) can be influenced by the use of immunosuppressants or not are still unclear.Objectives:The study aimed to explore the changes of lymphocyte subsets in patients of IIM with or without important organ infection, and the restoration of Th17/Treg after receiving low-dose IL-2.Methods:A total of 118 IIM patients were enrolled and classified into infection group and non-infection group based on the important organ infection. Of them, 48 cases were treated with low dose IL-2 (5.0*105IU for 5 days). The absolute number of peripheral total T, B, CD4+T, CD8+T, NK, Th1, Th2, Th17 and Treg cell subsets were analyzed by flow cytometry combined with absolute counting beads. Clinical data, laboratory examinations and the levels of peripheral lymphocyte subsets were analyzed retrospectively.Results:In these patients, especially in the infection group, the absolute number of T, CD4+T, CD8+T, NK, Th1, Th2, Th17 and Treg cells were significantly decreased as compared with that in the healthy controls, which were significantly increased by low dose IL-2 (especially Treg cells) treatment. The levels of ESR, LDH and HBDH and the ratio of Th17/Treg were significantly lower than those before IL-2 treatment (Z=-2.237, -2.083, -2.140, -3.663,P=0.025, 0.037, 0.032, 0.000). The 48 cases who received IL-2 treatment were divided into 2 groups according to whether they used immunosuppressants. There was no significant difference in the absolute number of T, B, CD4+T, CD8+T, Th1, Th2, Th17 and Treg cells, the proportion of Th17 and Treg cells and the ratio of Th17/Treg between the 2 groups (P>0.05).Conclusion:Global decrease in lymphocyte subsets was found in IIM patients, especially those who had important organ infection. A significant re-balance of Th17/Treg was observed after receiving treatment with low-dose IL-2. Furthermore, the restoration of lymphocyte subsets showed similar degree after treatment with or without immunosuppressants. Low-dose IL-2 may become a potential therapy for IIM patients. The mechanism of lymphocyte decrease in IIM is required further to study.References:[1]Clark K E N, Isenberg D A. A review of inflammatory idiopathic myopathy focusing on polymyositis[J]. European Journal of Neurology, 2017.[2]Tieu J, Lundberg IE, Limaye V. Idiopathic inflammatory myositis. Best Pract Res Clin Rheumatol. 2016. 30(1): 149-68.[3]Mandel DE, Malemud CJ, Askari AD. Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis. Int J Mol Sci. 2017. 18(5).[4]Zhang SX, Wang J, Sun HH, et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis. 2019 .[5]Espinosa-Ortega F, Gómez-Martin D, Santana-De Anda K, Romo-Tena J, Villaseñor-Ovies P, Alcocer-Varela J. Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets. Clin Exp Immunol. 2015. 179(3): 520-8.[6]Feng M, Guo H, Zhang C, et al. Absolute reduction of regulatory T cells and regulatory effect of short-term and low-dose IL-2 in polymyositis or dermatomyositis. Int Immunopharmacol. 2019. 77: 105912.Acknowledgments:Thanks for the support of my teachers, classmates and my family.Disclosure of Interests:None declared

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

scholarly journals The Complex Role of Regulatory T Cells in Immunity and Aging

2021 ◽  
Vol 11 ◽  
Author(s):  
Lourdes Rocamora-Reverte ◽  
Franz Leonard Melzer ◽  
Reinhard Würzner ◽  
Birgit Weinberger
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Γδt Cells ◽  
Cell Functions ◽  
Age Related ◽  
Self Antigens

The immune system is a tightly regulated network which allows the development of defense mechanisms against foreign antigens and tolerance toward self-antigens. Regulatory T cells (Treg) contribute to immune homeostasis by maintaining unresponsiveness to self-antigens and suppressing exaggerated immune responses. Dysregulation of any of these processes can lead to serious consequences. Classically, Treg cell functions have been described in CD4+ T cells, but other immune cells also harbour the capacity to modulate immune responses. Regulatory functions have been described for different CD8+ T cell subsets, as well as other T cells such as γδT cells or NKT cells. In this review we describe the diverse populations of Treg cells and their role in different scenarios. Special attention is paid to the aging process, which is characterized by an altered composition of immune cells. Treg cells can contribute to the development of various age-related diseases but they are poorly characterized in aged individuals. The huge diversity of cells that display immune modulatory functions and the lack of universal markers to identify Treg make the expanding field of Treg research complex and challenging. There are still many open questions that need to be answered to solve the enigma of regulatory T cells.

Inhibiting IL-2 Signaling and the Regulatory T-Cell Pathway Using Computationally Designed Novel Peptides

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3875-3875
Author(s):  
Tammy Price-Troska ◽  
David Diller ◽  
Alexander Bayden ◽  
Mark Jarosinski ◽  
Joseph Audies ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Function ◽  
Treg Cell ◽  
Immune Cell ◽  
Conflicts Of Interest ◽  
Interleukin 2 ◽  
Computational Design ◽  
Treg Cells ◽  
Cell Numbers

Abstract Regulatory T-cells (TREG) are the gateway to immune function and typically regulate immune cell activation. Cytokines, including interleukin-2 (IL-2), induce T-cell differentiation and promote a regulatory phenotype. Once activated via the IL-2 receptor (IL-2R), a cascade of events in T-cells initiate signal transducer and activator of transcription 5 (STAT5) and Forkhead box P3 (FOXP3) activation which appear to function as important regulators of this immunologic pathway and promote the development and function of TREG cells. In non-Hodgkin lymphoma (NHL), we have found that intratumoral TREG cells are increased in number and suppress immune function. In previous work, we have found that TREG cells inhibit T-cell proliferation, suppress cytokine production and limit effector cell cytotoxicity. We have also shown that increased serum levels of soluble sIL-2Rα is a prognostic factor in NHL and that sIL-2Rα can bind to IL-2 and promote its signaling thereby increasing TREG cell numbers. In this study, we developed a strategy to inhibit the binding of IL-2 to sIL-2Rα with the goal of suppressing the induction of FOXP3 and decreasing TREG cell numbers. To do this, we developed peptides designed to disrupt the interaction between IL2 and sILRα. In collaboration with CMDBioscienceSM, we developed and analyzed 22 peptide compounds derived by structure-based computational design. Initially, we screened each peptide at increasing concentrations using an ELISA assay to test the inhibition of IL-2/IL-2Rα binding by the solubilized peptide. Candidate peptides were then further tested using upregulation of pSTAT5 and FOXP3 in T-cells measured by flow cytometry as a measure of inhibition of IL-2 signaling. The peptides were developed according to different design hypotheses and grouped into different families; the screening ELISA results indicated 4 promising peptides that inhibited IL2/IL2Rα binding (up to 100% inhibition; max peptide concentration of 100uM). These peptides were then used to determine their effect on STAT5 and FOXP3 expression. A lead candidate peptide consistently reduced the expression of FOXP3 and STAT5 expression compared to cells not exposed to peptide. Use of the peptide to disrupt IL-2 signaling inhibited the development of cells with a TREG phenotype. We conclude that structure-based peptide design can be used to identify novel peptide inhibitors that block IL-2/IL-2Rα signaling and inhibit STAT5 and FOXP3 upregulation. These peptides could be used as new therapeutic agents to limit immune suppression by TREG cells and promote a more effective anti-tumor immune response in NHL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Evaluation of Thymic Output and Regulatory T Cells in Kidney Transplant Recipients with Chronic Antibody-Mediated Rejection

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Abbas Shahi ◽  
Saeedeh Salehi ◽  
Shima Afzali ◽  
Ladan Gol Mohammad Pour Afrakoti ◽  
Marzie Esmaeili ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Graft Function ◽  
Treg Cells ◽  
Kidney Transplant Recipients ◽  
Transplant Tolerance ◽  
Thymic Output ◽  
Antibody Mediated Rejection

Background. Regulatory T cells (Tregs) and recent thymic emigrants (RTEs) have an essential role in the regulation of allogeneic immune responses. However, their mechanisms of action in chronic antibody-mediated rejection (cAMR) are still unclear. In this study, we aimed to compare Treg and RTE levels between stable graft function (SGF) patients and cAMR subjects after kidney transplantation. Method. Mononuclear cells (MNs) were separated from peripheral blood, and flow cytometry analysis was performed for detection of CD4+ and CD25high as Treg markers and CD4+, CD31+, and CD45RA+ as RTE immunophenotyping markers. Result. The level of peripheral Treg cells was significantly lower in cAMR subjects in comparison to stable graft function patients. Moreover, SGF patients who had received cyclosporine A had a higher level of Treg in comparison to the tacrolimus recipients. Nevertheless, the RTE level between SGF and cAMR patients did not show any significant differences. Conclusion. It seems that Treg cells are significantly associated with transplant outcomes in cAMR patients, and prescribed immunosuppressive drugs can influence the frequency of this crucial subset of T cells. Although these drugs are beneficial and inevitable for allograft maintenance, more investigations are needed to elucidate their complete effects on different immune cell subsets which some of them like Tregs are in favor of transplant tolerance. Besides, the thymic output is seemingly not a beneficial biomarker for predicting cAMR; however, more in vivo and in vitro studies are needed for revealing the precise role of Tregs and RTEs in the transplantation context.

scholarly journals The Effects of TLR Activation on T-Cell Development and Differentiation

2012 ◽  
Vol 2012 ◽  
pp. 1-32 ◽  
Author(s):  
Bo Jin ◽  
Tao Sun ◽  
Xiao-Hong Yu ◽  
Ying-Xiang Yang ◽  
Anthony E. T. Yeo
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
T Cell Development ◽  
Cell Receptor ◽  
Treg Cells ◽  
Cell Development ◽  
T Cell Subsets ◽  
Follicular Helper ◽  
Development And Differentiation

Invading pathogens have unique molecular signatures that are recognized by Toll-like receptors (TLRs) resulting in either activation of antigen-presenting cells (APCs) and/or costimulation of T cells inducing both innate and adaptive immunity. TLRs are also involved in T-cell development and can reprogram Treg cells to become helper cells. T cells consist of various subsets, that is, Th1, Th2, Th17, T follicular helper (Tfh), cytotoxic T lymphocytes (CTLs), regulatory T cells (Treg) and these originate from thymic progenitor thymocytes. T-cell receptor (TCR) activation in distinct T-cell subsets with different TLRs results in differing outcomes, for example, activation of TLR4 expressed in T cells promotes suppressive function of regulatory T cells (Treg), while activation of TLR6 expressed in T cells abrogates Treg function. The current state of knowledge of regarding TLR-mediated T-cell development and differentiation is reviewed.

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