دورية أكاديمية
أعرض في EDS

Low-dose Interleukin-2 Therapy: Fine-tuning Treg in Solid Organ Transplantation?

التفاصيل البيبلوغرافية
العنوان: Low-dose Interleukin-2 Therapy: Fine-tuning Treg in Solid Organ Transplantation?
المؤلفون: Amini L; Berlin Center for Advanced Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health - Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany., Kaeda J; Berlin Center for Advanced Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany., Weber O; Institute of Molecular Medicine and Experimental Immunology (IMMEI), University of Bonn, Bonn, Germany., Reinke P; Berlin Center for Advanced Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health - Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
المصدر: Transplantation [Transplantation] 2024 Jul 01; Vol. 108 (7), pp. 1492-1508. Date of Electronic Publication: 2024 Jan 31.
نوع المنشور: Journal Article; Review
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0132144 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1534-6080 (Electronic) Linking ISSN: 00411337 NLM ISO Abbreviation: Transplantation Subsets: MEDLINE
أسماء مطبوعة: Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Williams & Wilkins.
مواضيع طبية MeSH: T-Lymphocytes, Regulatory*/immunology , T-Lymphocytes, Regulatory*/drug effects , Interleukin-2*/administration & dosage , Organ Transplantation*/adverse effects , Graft Rejection*/immunology , Graft Rejection*/prevention & control, Humans ; Animals ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/therapeutic use ; Graft Survival/drug effects ; Treatment Outcome
مستخلص: Regulatory T cells (Treg), a subset of CD4 + T cells, are potent regulators of immune reactions, which have been shown to be a promising therapeutic alternative to toxic immunosuppressive drugs. Data support the utility of Treg in managing immunopathologies, including solid organ transplant rejection, graft-versus-host disease, and autoimmune disorders. Notably, reports suggest that interleukin-2 (IL-2) is critical to survival of Treg, which constitutively express high levels of CD25, that is, the IL-2 receptor α-chain, and are exquisitely sensitive to IL-2, even at very low concentrations in contrast to effector T cells, which only upregulate IL-2 receptor α-chain on activation. This has led to the notion of using low doses of exogenous IL-2 therapeutically to modulate the immune system, specifically Treg numbers and function. Here, we summarize developments of clinical experience with low-dose IL-2 (LD-IL-2) as a therapeutic agent. So far, no clinical data are available to support the therapeutic use of LD-IL-2 therapy in the solid organ transplant setting. For the latter, fine-tuning by biotechnological approaches may be needed because of the narrow therapeutic window and off-target effects of LD-IL-2 therapy and so to realize the therapeutic potential of this molecule.
Competing Interests: The authors declare no conflicts of interest.
(Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
References: Qureshi OS, Zheng Y, Nakamura K, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332:600–603.
Akkaya B, Oya Y, Akkaya M, et al. Regulatory T cells mediate specific suppression by depleting peptide-MHC class II from dendritic cells. Nat Immunol. 2019;20:218–231.
Li Y, Li XC, Zheng XX, et al. Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance. Nat Med. 1999;5:1298–1302.
Zeiser R, Nguyen VH, Beilhack A, et al. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood. 2006;108:390–399.
Whitehouse G, Gray E, Mastoridis S, et al. IL-2 therapy restores regulatory T-cell dysfunction induced by calcineurin inhibitors. Proc Natl Acad Sci U S A. 2017;114:7083–7088.
San Segundo D, Ruiz JC, Fernandez-Fresnedo G, et al. Calcineurin inhibitors affect circulating regulatory T cells in stable renal transplant recipients. Transplant Proc. 2006;38:2391–2393.
Presser D, Sester U, Mohrbach J, et al. Differential kinetics of effector and regulatory T cells in patients on calcineurin inhibitor-based drug regimens. Kidney Int. 2009;76:557–566.
Hermann-Kleiter N, Baier G. NFAT pulls the strings during CD4+ T helper cell effector functions. Blood. 2010;115:2989–2997.
Alvarez Salazar EK, Cortes-Hernandez A, Aleman-Muench GR, et al. Methylation of FOXP3 TSDR underlies the impaired suppressive function of Tregs from long-term belatacept-treated kidney transplant patients. Front Immunol. 2017;8:219.
Akimova T, Kamath BM, Goebel JW, et al. Differing effects of rapamycin or calcineurin inhibitor on T-regulatory cells in pediatric liver and kidney transplant recipients. Am J Transplant. 2012;12:3449–3461.
Taubert R, Danger R, Londono MC, et al. Hepatic infiltrates in operational tolerant patients after liver transplantation show enrichment of regulatory T cells before proinflammatory genes are downregulated. Am J Transplant. 2016;16:1285–1293.
Matsuoka K, Kim HT, McDonough S, et al. Altered regulatory T cell homeostasis in patients with CD4+ lymphopenia following allogeneic hematopoietic stem cell transplantation. J Clin Invest. 2010;120:1479–1493.
Murase K, Kim HT, Bascug OR, et al. Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation. Haematologica. 2014;99:1499–1508.
Kawano Y, Kim HT, Matsuoka K, et al. Low telomerase activity in CD4+ regulatory T cells in patients with severe chronic GVHD after hematopoietic stem cell transplantation. Blood. 2011;118:5021–5030.
Matsuoka K, Koreth J, Kim HT, et al. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. Sci Transl Med. 2013;5:179–ra43.
Berntsen A, Brimnes MK, thor Straten P, et al. Increase of circulating CD4+CD25 high FoxP3 + regulatory T cells in patients with metastatic renal cell carcinoma during treatment with dendritic cell vaccination and low-dose interleukin-2. J Immunother. 2010;33:425–434.
Caudy AA, Reddy ST, Chatila T, et al. CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes. J Allergy Clin Immunol. 2007;119:482–487.
Sharfe N, Dadi HK, Shahar M, et al. Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor. Proc Natl Acad Sci U S A. 1997;94:3168–3171.
von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 2016;75:1407–1415.
Vocanson M, Rozieres A, Hennino A, et al. Inducible costimulator (ICOS) is a marker for highly suppressive antigen-specific T cells sharing features of TH17/TH1 and regulatory T cells. J Allergy Clin Immunol. 2010;126:280–9, 289.e1.
Hirakawa M, Matos TR, Liu H, et al. Low-dose IL-2 selectively activates subsets of CD4(+) Tregs and NK cells. JCI Insight. 2016;1:e89278.
Yu A, Snowhite I, Vendrame F, et al. Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic mechanisms supports the use of low-dose IL-2 therapy in type 1 diabetes. Diabetes. 2015;64:2172–2183.
Lam AJ, Uday P, Gillies JK, et al. Helios is a marker, not a driver, of human Treg stability. Eur J Immunol. 2022;52:75–84.
Krieg C, Letourneau S, Pantaleo G, et al. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci U S A. 2010;107:11906–11911.
Murakami N, Borges TJ, Thet Su Win TS, et al. Low-dose interleukin-2 promotes immune regulation in face transplantation: a pilot study. Am J Transplant. 2023;23:549–558.
Boyman O, Kovar M, Rubinstein MP, et al. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science. 2006;311:1924–1927.
Yan JJ, Lee JG, Jang JY, et al. IL-2/anti-IL-2 complexes ameliorate lupus nephritis by expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cells. Kidney Int. 2017;91:603–615.
Ito S, Battiwalla M, Melenhorst JJ, et al. Ultra-low dose IL-2 safely expands regulatory T cells and CD56bright NK cells in healthy volunteers: towards safer stem cell donors? Blood. 2012;120:3283–3283.
Ito S, Bollard CM, Carlsten M, et al. Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory T cells and natural killer cells in healthy volunteers. Mol Ther. 2014;22:1388–1395.
Zorn E, Nelson EA, Mohseni M, et al. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood. 2006;108:1571–1579.
Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011;365:2067–2077.
Artillo S, Pastore G, Alberti A, et al. Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B. J Med Virol. 1998;54:167–172.
Kakumu S, Fuji A, Yoshioka K, et al. Pilot study of recombinant human interleukin 2 for chronic type B hepatitis. Hepatology. 1988;8:487–492.
Tilg H, Vogel W, Tratkiewicz J, et al. Pilot study of natural human interleukin-2 in patients with chronic hepatitis B. J Hepatol. 1993;19:259–267.
Hartemann A, Bensimon G, Payan CA, et al. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2013;1:295–305.
Rosenzwajg M, Churlaud G, Mallone R, et al. Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients. J Autoimmun. 2015;58:48–58.
Todd JA, Evangelou M, Cutler AJ, et al. Regulatory T cell responses in participants with type 1 diabetes after a single dose of interleukin-2: a non-randomised, open label, adaptive dose-finding trial. PLoS Med. 2016;13:e1002139.
Waldron-Lynch F, Kareclas P, Irons K, et al. Rationale and study design of the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial. BMJ Open. 2014;4:e005559.
Seelig E, Howlett J, Porter L, et al. The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in patients with type 1 diabetes. JCI Insight. 2018;3:e99306.
Truman LA, Pekalski ML, Kareclas P, et al. Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study. BMJ Open. 2015;5:e009799.
Humrich JY, von Spee-Mayer C, Siegert E, et al. Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis. 2015;74:791–792.
He J, Zhang X, Wei Y, et al. Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus. Nat Med. 2016;22:991–993.
He J, Zhang R, Shao M, et al. Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2020;79:141–149.
Humrich JY, Cacoub P, Rosenzwajg M, et al. Low-dose interleukin-2 therapy in active systemic lupus erythematosus (LUPIL-2): a multicentre, double-blind, randomised and placebo-controlled phase II trial. Ann Rheum Dis. 2022;81:1685–1694.
Castela E, Le Duff F, Butori C, et al. Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata. JAMA Dermatol. 2014;150:748–751.
Lim TY, Martinez-Llordella M, Kodela E, et al. Low-dose interleukin-2 for refractory autoimmune hepatitis. Hepatology. 2018;68:1649–1652.
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. 2021;80:e130.
Miao M, Hao Z, Guo Y, et al. Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjogren’s syndrome. Ann Rheum Dis. 2018;77:1838–1840.
Wang J, Zhang SX, Hao YF, et al. The numbers of peripheral regulatory T cells are reduced in patients with psoriatic arthritis and are restored by low-dose interleukin-2. Ther Adv Chronic Dis. 2020;11:2040622320916014.
Allegretti J, Canavan J, Mitsialis V, et al. Low dose Il-2 for the treatment of moderate to severe ulcerative colitis. Gastroenterology. 2021;160:S9–S10.
Rosenzwajg M, Lorenzon R, Cacoub P, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019;78:209–217.
Camu W, Mickunas M, Veyrune JL, et al. Repeated 5-day cycles of low dose aldesleukin in amyotrophic lateral sclerosis (IMODALS): a phase 2a randomised, double-blind, placebo-controlled trial. EBioMedicine. 2020;59:102844.
Zhao TX, Kostapanos M, Griffiths C, et al. Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS): protocol and study rationale for a randomised, double-blind, placebo-controlled, phase I/II clinical trial. BMJ Open. 2018;8:e022452.
Zhao TX, Sriranjan RS, Lu Y, et al. Low dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndrome (LILACS). Eur Heart J. 2020;41:ehaa946.1735.
Zhao TX, Sriranjan RS, Tuong ZK, et al. Regulatory T-cell response to low-dose interleukin-2 in ischemic heart disease. NEJM Evidence. 2022;1:1–11.
Woodson EM, Chianese-Bullock KA, Wiernasz CJ, et al. Assessment of the toxicities of systemic low-dose interleukin-2 administered in conjunction with a melanoma peptide vaccine. J Immunother. 2004;27:380–388.
Donckier V, Craciun L, Lucidi V, et al. Acute liver transplant rejection upon immunosuppression withdrawal in a tolerance induction trial: potential role of IFN-gamma-secreting CD8+ T cells. Transplantation. 2009;87:S91–S95.
Boyer O, Saadoun D, Abriol J, et al. CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood. 2004;103:3428–3430.
Landau DA, Rosenzwajg M, Saadoun D, et al. Correlation of clinical and virologic responses to antiviral treatment and regulatory T cell evolution in patients with hepatitis C virus-induced mixed cryoglobulinemia vasculitis. Arthritis Rheum. 2008;58:2897–2907.
Collison J. Low-dose IL-2 therapy for autoimmune diseases. Nat Rev Rheumatol. 2019;15:2.
Wigren M, Bjorkbacka H, Andersson L, et al. Low levels of circulating CD4+FoxP3+ T cells are associated with an increased risk for development of myocardial infarction but not for stroke. Arterioscler Thromb Vasc Biol. 2012;32:2000–2004.
Soiffer RJ, Murray C, Cochran K, et al. Clinical and immunologic effects of prolonged infusion of low-dose recombinant interleukin-2 after autologous and T-cell-depleted allogeneic bone marrow transplantation. Blood. 1992;79:517–526.
Gottlieb DJ, Prentice HG, Heslop HE, et al. IL-2 infusion abrogates humoral immune responses in humans. Clin Exp Immunol. 1992;87:493–498.
Soiffer RJ, Murray C, Gonin R, et al. Effect of low-dose interleukin-2 on disease relapse after T-cell- depleted allogeneic bone marrow transplantation. Blood. 1994;84:964–971.
Lopez-Jimenez J, Perez-Oteyza J, Munoz A, et al. Subcutaneous versus intravenous low-dose IL-2 therapy after autologous transplantation: results of a prospective, non-randomized study. Bone Marrow Transplant. 1997;19:429–434.
Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365:2055–2066.
Koreth J, Kim HT, Jones KT, et al. Efficacy, durability, and response predictors of low-dose interleukin-2 therapy for chronic graft-versus-host disease. Blood. 2016;128:130–137.
Whangbo JS, Kim HT, Nikiforow S, et al. Functional analysis of clinical response to low-dose IL-2 in patients with refractory chronic graft-versus-host disease. Blood Adv. 2019;3:984–994.
Kennedy-Nasser AA, Ku S, Castillo-Caro P, et al. Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation mediates expansion of regulatory T cells without diminishing antiviral and antileukemic activity. Clin Cancer Res. 2014;20:2215–2225.
Zhao XY, Zhao XS, Wang YT, et al. Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: a randomized study. Oncoimmunology. 2016;5:e1250992.
Whangbo JS, Kim HT, Mirkovic N, et al. Dose-escalated interleukin-2 therapy for refractory chronic graft-versus-host disease in adults and children. Blood Adv. 2019;3:2550–2561.
Kim HT, Koreth J, Whangbo J, et al. Organ-specific response after low-dose interleukin-2 therapy for steroid-refractory chronic graft-versus-host disease. Blood Adv. 2022;6:4392–4402.
Webster KE, Walters S, Kohler RE, et al. In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J Exp Med. 2009;206:751–760.
Hu M, Hawthorne WJ, Nicholson L, et al. Low-dose interleukin-2 combined with rapamycin led to an expansion of CD4(+)CD25(+)FOXP3(+) regulatory T cells and prolonged human islet allograft survival in humanized mice. Diabetes. 2020;69:1735–1748.
Tahvildari M, Omoto M, Chen Y, et al. In vivo expansion of regulatory T cells by low-dose interleukin-2 treatment increases allograft survival in corneal transplantation. Transplantation. 2016;100:525–532.
Ravichandran R, Itabashi Y, Fleming T, et al. Low-dose IL-2 prevents murine chronic cardiac allograft rejection: role for IL-2-induced T regulatory cells and exosomes with PD-L1 and CD73. Am J Transplant. 2022;22:2180–2194.
Yamada Y, Nadazdin O, Boskovic S, et al. Repeated injections of IL-2 break renal allograft tolerance induced via mixed hematopoietic chimerism in monkeys. Am J Transplant. 2015;15:3055–3066.
Lim TY, Perpinan E, Londono MC, et al. Low dose interleukin-2 selectively expands circulating regulatory T cells but fails to promote liver allograft tolerance in humans. J Hepatol. 2023;78:153–164.
Belizaire R, Kim HT, Poryanda SJ, et al. Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease. Blood Adv. 2019;3:969–979.
Zhao C, Chu Y, Liang Z, et al. Low dose of IL-2 combined with rapamycin restores and maintains the long-term balance of Th17/Treg cells in refractory SLE patients. BMC Immunol. 2019;20:32.
Whangbo J, Nikiforow S, Kim HT, et al. A phase 1 study of donor regulatory T-cell infusion plus low-dose interleukin-2 for steroid-refractory chronic graft-vs-host disease. Blood Adv. 2022;6:5786–5796.
Theil A, Tuve S, Oelschlagel U, et al. Adoptive transfer of allogeneic regulatory T cells into patients with chronic graft-versus-host disease. Cytotherapy. 2015;17:473–486.
Dong S, Hiam-Galvez KJ, Mowery CT, et al. The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes. JCI Insight. 2021;6:e147474.
Arno A, Ruiz L, Juan M, et al. Efficacy of low-dose subcutaneous interleukin-2 to treat advanced human immunodeficiency virus type 1 in persons with ≤250/µL CD4 T cells and undetectable plasma virus load. J Infect Dis. 1999;180:56–60.
Amendola A, Poccia F, Martini F, et al. Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration. Clin Exp Immunol. 2000;120:324–332.
Lalezari JP, Beal JA, Ruane PJ, et al. Low-dose daily subcutaneous interleukin-2 in combination with highly active antiretroviral therapy in HIV+ patients: a randomized controlled trial. HIV Clin Trials. 2000;1:1–15.
Vogler MA, Teppler H, Gelman R, et al.; AIDS Clinical Trials Group 248 Study Team. Daily low-dose subcutaneous interleukin-2 added to single- or dual-nucleoside therapy in HIV infection does not protect against CD4+ T-cell decline or improve other indices of immune function: results of a randomized controlled clinical trial (ACTG 248). J Acquir Immune Defic Syndr. 2004;36:576–587.
Bruch HR, Korn A, Klein H, et al. Treatment of chronic hepatitis B with interferon α-2b and interleukin-2. J Hepatol. 1993;17:S52–S55.
Johnson JL, Ssekasanvu E, Okwera A, et al.; Uganda-Case Western Reserve University Research Collaboration. Randomized trial of adjunctive interleukin-2 in adults with pulmonary tuberculosis. Am J Respir Crit Care Med. 2003;168:185–191.
Perillo A, Pierelli L, Battaglia A, et al. Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer. Bone Marrow Transplant. 2002;30:571–578.
Mendez-Lagares G, Jaramillo-Ruiz D, Pion M, et al. HIV infection deregulates the balance between regulatory T cells and IL-2-producing CD4 T cells by decreasing the expression of the IL-2 receptor in Treg. J Acquir Immune Defic Syndr. 2014;65:278–282.
Teppler H, Kaplan G, Smith K, et al. Efficacy of low doses of the polyethylene glycol derivative of interleukin-2 in modulating the immune response of patients with human immunodeficiency virus type 1 infection. J Infect Dis. 1993;167:291–298.
Teppler H, Kaplan G, Smith KA, et al. Prolonged immunostimulatory effect of low-dose polyethylene glycol interleukin 2 in patients with human immunodeficiency virus type 1 infection. J Exp Med. 1993;177:483–492.
Fanton C, Siddhanti S, Dixit N, et al. OP0195 Selective expansion of regulatory T-cells in humans by a novel IL-2 conjugate T-reg stimulator, NKTR-358, being developed for the treatment of autoimmune diseases. Ann Rheum Dis. 2019;78:172–173.
Tchao N, Gorski KS, Yuraszeck T, et al. Amg 592 Is an investigational IL-2 mutein that induces highly selective expansion of regulatory T cells. Blood. 2017;130:696–696.
Tchao N, Sarkar N, Hu X, et al. Ab0432 Efavaleukin alfa, a novel Il-2 mutein, selectively expands regulatory T cells in patients with SLE: final results of a phase 1b multiple ascending dose study. Ann Rheum Dis. 2022;81:1343.3–131344.
Meyers FJ, Paradise C, Scudder SA, et al. A phase I study including pharmacokinetics of polyethylene glycol conjugated interleukin-2. Clin Pharmacol Ther. 1991;49:307–313.
Dixit N, Fanton C, Langowski JL, et al. NKTR-358: a novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases. J Transl Autoimmun. 2021;4:100103.
Bell CJ, Sun Y, Nowak UM, et al. Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells. J Autoimmun. 2015;56:66–80.
Zhou P, Chen J, He J, et al. Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus. PLoS Pathog. 2021;17:e1009858.
Peterson LB, Bell CJM, Howlett SK, et al. A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease. J Autoimmun. 2018;95:1–14.
Trotta E, Bessette PH, Silveria SL, et al. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism. Nat Med. 2018;24:1005–1014.
Kildey K, Francis RS, Hultin S, et al. Specialized roles of human natural killer cell subsets in kidney transplant rejection. Front Immunol. 2019;10:1877.
Yazdani S, Callemeyn J, Gazut S, et al. Natural killer cell infiltration is discriminative for antibody-mediated rejection and predicts outcome after kidney transplantation. Kidney Int. 2019;95:188–198.
Benitez C, Londono MC, Miquel R, et al. Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients. Hepatology. 2013;58:1824–1835.
Mathew JM, H-Voss J, LeFever A, et al. A phase I clinical trial with ex vivo expanded recipient regulatory T cells in living donor kidney transplants. Sci Rep. 2018;8:7428.
Roemhild A, Otto NM, Moll G, et al. Regulatory T cells for minimising immune suppression in kidney transplantation: phase I/IIa clinical trial. BMJ. 2020;371:m3734.
Tang Q, Leung J, Peng Y, et al. Autologous donor-alloantigen reactive Treg cell therapy for minimization of immunosuppression after liver transplantation. Sci Transl Med. 2022;14:eabo2628.
Amini L, Greig J, Schmueck-Henneresse M, et al. Super-Treg: toward a new era of adoptive Treg therapy enabled by genetic modifications. Front Immunol. 2021;11:611638.
Ottolenghi A, Bolel P, Sarkar R, et al. Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity. Sci Rep. 2021;11:7676.
Chandran S, Tang Q, Sarwal M, et al. Polyclonal regulatory T cell therapy for control of inflammation in kidney transplants. Am J Transplant. 2017;17:2945–2954.
Kmieciak M, Gowda M, Graham L, et al. Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function. J Transl Med. 2009;7:89.
Wang J, Ioan-Facsinay A, van der Voort EI, et al. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol. 2007;37:129–138.
Pillai V, Ortega SB, Wang CK, et al. Transient regulatory T-cells: a state attained by all activated human T-cells. Clin Immunol. 2007;123:18–29.
Baan CC, van der Mast BJ, Klepper M, et al. Differential effect of calcineurin inhibitors, anti-CD25 antibodies and rapamycin on the induction of FOXP3 in human T cells. Transplantation. 2005;80:110110–110117.
معلومات مُعتمدة: 825392 EU
المشرفين على المادة: 0 (Interleukin-2)
0 (Immunosuppressive Agents)
تواريخ الأحداث: Date Created: 20240131 Date Completed: 20240625 Latest Revision: 20240712
رمز التحديث: 20240712
مُعرف محوري في PubMed: PMC11188637
DOI: 10.1097/TP.0000000000004866
PMID: 38294829
قاعدة البيانات: MEDLINE
الوصف
تدمد:1534-6080
DOI:10.1097/TP.0000000000004866