{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T23:45:52Z","timestamp":1783208752104,"version":"3.54.6"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G.0316.25N"],"award-info":[{"award-number":["G.0316.25N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G.0667.21N"],"award-info":[{"award-number":["G.0667.21N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G.0C63.19N"],"award-info":[{"award-number":["G.0C63.19N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["I.0018.22N"],"award-info":[{"award-number":["I.0018.22N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C1\/18\/006"],"award-info":[{"award-number":["C1\/18\/006"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C16\/24\/012"],"award-info":[{"award-number":["C16\/24\/012"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["KA\/20\/077"],"award-info":[{"award-number":["KA\/20\/077"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1007\/s00125-025-06604-2","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T03:57:31Z","timestamp":1763611051000},"page":"466-479","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Redosing of anti-CD3 antibodies in NOD mice with new-onset diabetes does not alter the effect of a single treatment course"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2624-8154","authenticated-orcid":false,"given":"Amber","family":"Wouters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-8685","authenticated-orcid":false,"given":"Pierre","family":"Lemaitre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-6103","authenticated-orcid":false,"given":"Laure","family":"Degroote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke","family":"Viaene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7525-7991","authenticated-orcid":false,"given":"Marc","family":"Packbier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-1072","authenticated-orcid":false,"given":"Nick","family":"Geukens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4055-5233","authenticated-orcid":false,"given":"Chantal","family":"Mathieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-6089","authenticated-orcid":false,"given":"Conny","family":"Gysemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"issue":"1","key":"6604_CR1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1152\/physrev.00003.2010","volume":"91","author":"TL van Belle","year":"2011","unstructured":"van Belle TL, Coppieters KT, von Herrath MG (2011) Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 91(1):79\u2013118. https:\/\/doi.org\/10.1152\/physrev.00003.2010","journal-title":"Physiol Rev"},{"issue":"10","key":"6604_CR2","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/S2213-8587(22)00218-2","volume":"10","author":"GA Gregory","year":"2022","unstructured":"Gregory GA, Robinson TIG, Linklater SE et al (2022) Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. Lancet Diabetes Endocrinol 10(10):741\u2013760. https:\/\/doi.org\/10.1016\/S2213-8587(22)00218-2","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"7","key":"6604_CR3","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1056\/NEJMoa1902226","volume":"381","author":"KC Herold","year":"2019","unstructured":"Herold KC, Bundy BN, Long SA et al (2019) An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med 381(7):603\u2013613. https:\/\/doi.org\/10.1056\/NEJMoa1902226","journal-title":"N Engl J Med"},{"issue":"4","key":"6604_CR4","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s00125-018-4786-9","volume":"62","author":"AL Perdigoto","year":"2019","unstructured":"Perdigoto AL, Preston-Hurlburt P, Clark P et al (2019) Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia 62(4):655\u2013664. https:\/\/doi.org\/10.1007\/s00125-018-4786-9","journal-title":"Diabetologia"},{"issue":"583","key":"6604_CR5","doi-asserted-by":"publisher","first-page":"eabc8980","DOI":"10.1126\/scitranslmed.abc8980","volume":"13","author":"EK Sims","year":"2021","unstructured":"Sims EK, Bundy BN, Stier K et al (2021) Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med 13(583):eabc8980. https:\/\/doi.org\/10.1126\/scitranslmed.abc8980","journal-title":"Sci Transl Med"},{"issue":"9790","key":"6604_CR6","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/S0140-6736(11)60931-8","volume":"378","author":"N Sherry","year":"2011","unstructured":"Sherry N, Hagopian W, Ludvigsson J et al (2011) Teplizumab for treatment of type 1 diabetes (Prot\u00e9g\u00e9 study): 1-year results from a randomised, placebo-controlled trial. Lancet 378(9790):487\u2013497. https:\/\/doi.org\/10.1016\/S0140-6736(11)60931-8","journal-title":"Lancet"},{"issue":"11","key":"6604_CR7","doi-asserted-by":"publisher","first-page":"3766","DOI":"10.2337\/db13-0345","volume":"62","author":"KC Herold","year":"2013","unstructured":"Herold KC, Gitelman SE, Ehlers MR et al (2013) Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes 62(11):3766\u20133774. https:\/\/doi.org\/10.2337\/db13-0345","journal-title":"Diabetes"},{"issue":"23","key":"6604_CR8","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1056\/NEJMoa2308743","volume":"389","author":"EL Ramos","year":"2023","unstructured":"Ramos EL, Dayan CM, Chatenoud L et al (2023) Teplizumab and \u03b2-cell function in newly diagnosed type 1 diabetes. N Engl J Med 389(23):2151\u20132161. https:\/\/doi.org\/10.1056\/NEJMoa2308743","journal-title":"N Engl J Med"},{"issue":"22","key":"6604_CR9","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1056\/NEJMoa012864","volume":"346","author":"KC Herold","year":"2002","unstructured":"Herold KC, Hagopian W, Auger JA et al (2002) Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 346(22):1692\u20131698. https:\/\/doi.org\/10.1056\/NEJMoa012864","journal-title":"N Engl J Med"},{"issue":"5","key":"6604_CR10","doi-asserted-by":"publisher","first-page":"eaai7793","DOI":"10.1126\/sciimmunol.aai7793","volume":"1","author":"SA Long","year":"2016","unstructured":"Long SA, Thorpe J, DeBerg HA et al (2016) Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci Immunol 1(5):eaai7793. https:\/\/doi.org\/10.1126\/sciimmunol.aai7793","journal-title":"Sci Immunol"},{"key":"6604_CR11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.cellimm.2017.07.007","volume":"319","author":"SA Long","year":"2017","unstructured":"Long SA, Thorpe J, Herold KC et al (2017) Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes. Cell Immunol 319:3\u20139. https:\/\/doi.org\/10.1016\/j.cellimm.2017.07.007","journal-title":"Cell Immunol"},{"issue":"18","key":"6604_CR12","doi-asserted-by":"publisher","first-page":"e177492","DOI":"10.1172\/JCI177492","volume":"134","author":"A Lled\u00f3-Delgado","year":"2024","unstructured":"Lled\u00f3-Delgado A, Preston-Hurlburt P, Currie S et al (2024) Teplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes. J Clin Invest 134(18):e177492. https:\/\/doi.org\/10.1172\/JCI177492","journal-title":"J Clin Invest"},{"issue":"4","key":"6604_CR13","doi-asserted-by":"publisher","first-page":"103492","DOI":"10.1016\/j.xpro.2024.103492","volume":"5","author":"P Lemaitre","year":"2024","unstructured":"Lemaitre P, Mathieu C, Gysemans C (2024) Protocol for murine multi-tissue deep immunophenotyping using a 40-color full-spectrum flow cytometry panel. STAR Protoc 5(4):103492. https:\/\/doi.org\/10.1016\/j.xpro.2024.103492","journal-title":"STAR Protoc"},{"issue":"2","key":"6604_CR14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1002\/cpt.2432","volume":"112","author":"A-CD Dunvald","year":"2022","unstructured":"Dunvald A-CD, J\u00e4rvinen E, Mortensen C, Stage TB (2022) Clinical and molecular perspectives on inflammation-mediated regulation of drug metabolism and transport. Clin Pharmacol Therapeut 112(2):277\u2013290. https:\/\/doi.org\/10.1002\/cpt.2432","journal-title":"Clin Pharmacol Therapeut"},{"issue":"11","key":"6604_CR15","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1007\/s40262-022-01173-8","volume":"61","author":"M Gatti","year":"2022","unstructured":"Gatti M, Pea F (2022) The cytokine release syndrome and\/or the proinflammatory cytokines as underlying mechanisms of downregulation of drug metabolism and drug transport: a systematic review of the clinical pharmacokinetics of victim drugs of this drug-disease interaction under different clinical conditions. Clin Pharmacokinet 61(11):1519\u20131544. https:\/\/doi.org\/10.1007\/s40262-022-01173-8","journal-title":"Clin Pharmacokinet"},{"issue":"15","key":"6604_CR16","doi-asserted-by":"publisher","first-page":"6335","DOI":"10.1073\/pnas.0701171104","volume":"104","author":"S You","year":"2007","unstructured":"You S, Leforban B, Garcia C, Bach JF, Bluestone JA, Chatenoud L (2007) Adaptive TGF-\u03b2-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment. Proc Natl Acad Sci U S A 104(15):6335\u20136340. https:\/\/doi.org\/10.1073\/pnas.0701171104","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"6604_CR17","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1073\/pnas.91.1.123","volume":"91","author":"L Chatenoud","year":"1994","unstructured":"Chatenoud L, Thervet E, Primo J, Bach JF (1994) Anti-CD3 antibody induces long-term remission of overt autoimmunity in non-obese diabetic mice. Proc Natl Acad Sci U S A 91(1):123\u2013127. https:\/\/doi.org\/10.1073\/pnas.91.1.123","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"6604_CR18","doi-asserted-by":"publisher","first-page":"448","DOI":"10.2337\/db15-1625","volume":"66","author":"T Takiishi","year":"2016","unstructured":"Takiishi T, Cook DP, Korf H et al (2016) Reversal of diabetes in NOD mice by clinical-grade proinsulin and IL-10\u2013secreting Lactococcus lactis in combination with low-dose anti-CD3 depends on the induction of Foxp3-positive T cells. Diabetes 66(2):448\u2013459. https:\/\/doi.org\/10.2337\/db15-1625","journal-title":"Diabetes"},{"issue":"8","key":"6604_CR19","doi-asserted-by":"publisher","first-page":"2876","DOI":"10.2337\/db13-1236","volume":"63","author":"S Robert","year":"2014","unstructured":"Robert S, Gysemans C, Takiishi T et al (2014) Oral delivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcus lactis reverses diabetes in recent-onset NOD mice. Diabetes 63(8):2876\u20132887. https:\/\/doi.org\/10.2337\/db13-1236","journal-title":"Diabetes"},{"issue":"11","key":"6604_CR20","doi-asserted-by":"publisher","first-page":"3901","DOI":"10.2337\/db13-0236","volume":"62","author":"W Hagopian","year":"2013","unstructured":"Hagopian W, Ferry RJ Jr, Sherry N et al (2013) Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Prot\u00e9g\u00e9 trial. Diabetes 62(11):3901\u20133908. https:\/\/doi.org\/10.2337\/db13-0236","journal-title":"Diabetes"},{"issue":"5","key":"6604_CR21","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.4049\/jimmunol.1401551","volume":"194","author":"A Valle","year":"2015","unstructured":"Valle A, Barbagiovanni G, Jofra T et al (2015) Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation. J Immunol 194(5):2117\u20132127. https:\/\/doi.org\/10.4049\/jimmunol.1401551","journal-title":"J Immunol"},{"key":"6604_CR22","doi-asserted-by":"publisher","first-page":"1204363","DOI":"10.3389\/fimmu.2023.1204363","volume":"14","author":"Q Guan","year":"2023","unstructured":"Guan Q, Han M, Guo Q et al (2023) Strategies to reinvigorate exhausted CD8+ T cells in tumor microenvironment. Front Immunol 14:1204363. https:\/\/doi.org\/10.3389\/fimmu.2023.1204363","journal-title":"Front Immunol"},{"issue":"6","key":"6604_CR23","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1016\/j.cmet.2024.05.001","volume":"36","author":"M Ben Nasr","year":"2024","unstructured":"Ben Nasr M, Usuelli V, Dellepiane S et al (2024) Glucagon-like peptide 1 receptor is a T cell-negative costimulatory molecule. Cell Metab 36(6):1302\u20131319. https:\/\/doi.org\/10.1016\/j.cmet.2024.05.001","journal-title":"Cell Metab"},{"issue":"5","key":"6604_CR24","doi-asserted-by":"publisher","first-page":"599","DOI":"10.2337\/db22-0784","volume":"72","author":"T Wei","year":"2023","unstructured":"Wei T, Cui X, Jiang Y et al (2023) Glucagon acting at the GLP-1 receptor contributes to \u03b2-cell regeneration induced by glucagon receptor antagonism in diabetic mice. Diabetes 72(5):599\u2013610. https:\/\/doi.org\/10.2337\/db22-0784","journal-title":"Diabetes"},{"key":"6604_CR25","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1146\/annurev.immunol.19.1.683","volume":"19","author":"KW Moore","year":"2001","unstructured":"Moore KW, de Waal Malefyt R, Coffman RL, O\u2019Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683\u2013765. https:\/\/doi.org\/10.1146\/annurev.immunol.19.1.683","journal-title":"Annu Rev Immunol"},{"issue":"1","key":"6604_CR26","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1002\/eji.201545708","volume":"46","author":"JE Tooley","year":"2016","unstructured":"Tooley JE, Vudattu N, Choi J et al (2016) Changes in T-cell subsets identify responders to FcR-nonbinding anti-CD3 mAb (teplizumab) in patients with type 1 diabetes. Eur J Immunol 46(1):230\u2013241. https:\/\/doi.org\/10.1002\/eji.201545708","journal-title":"Eur J Immunol"},{"key":"6604_CR27","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.3389\/fimmu.2017.01124","volume":"8","author":"S Paul","year":"2017","unstructured":"Paul S, Lal G (2017) The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol 8:1124. https:\/\/doi.org\/10.3389\/fimmu.2017.01124","journal-title":"Front Immunol"},{"issue":"12","key":"6604_CR28","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/s41573-024-01051-x","volume":"23","author":"PJ Carter","year":"2024","unstructured":"Carter PJ, Quarmby V (2024) Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics. Nat Rev Drug Discov 23(12):898\u2013913. https:\/\/doi.org\/10.1038\/s41573-024-01051-x","journal-title":"Nat Rev Drug Discov"},{"issue":"6","key":"6604_CR29","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s40259-021-00507-5","volume":"35","author":"SJ Bots","year":"2021","unstructured":"Bots SJ, Parker CE, Brandse JF et al (2021) Anti-drug antibody formation against biologic agents in inflammatory bowel disease: a systematic review and meta-analysis. BioDrugs 35(6):715\u2013733. https:\/\/doi.org\/10.1007\/s40259-021-00507-5","journal-title":"BioDrugs"},{"issue":"8","key":"6604_CR30","doi-asserted-by":"publisher","first-page":"889","DOI":"10.2217\/imt-2016-0049","volume":"8","author":"C Kuhn","year":"2016","unstructured":"Kuhn C, Weiner HL (2016) Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside. Immunotherapy 8(8):889\u2013906. https:\/\/doi.org\/10.2217\/imt-2016-0049","journal-title":"Immunotherapy"},{"issue":"3","key":"6604_CR31","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.clim.2013.05.001","volume":"149","author":"AG Daifotis","year":"2013","unstructured":"Daifotis AG, Koenig S, Chatenoud L, Herold KC (2013) Anti-CD3 clinical trials in type 1 diabetes mellitus. Clin Immunol 149(3):268\u2013278. https:\/\/doi.org\/10.1016\/j.clim.2013.05.001","journal-title":"Clin Immunol"},{"issue":"4","key":"6604_CR32","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1900\/RDS.2012.9.372","volume":"9","author":"L Chatenoud","year":"2012","unstructured":"Chatenoud L, Waldmann H (2012) CD3 monoclonal antibodies: a first step towards operational immune tolerance in the clinic. Rev Diabet Stud 9(4):372\u2013381. https:\/\/doi.org\/10.1900\/RDS.2012.9.372","journal-title":"Rev Diabet Stud"},{"key":"6604_CR33","doi-asserted-by":"publisher","first-page":"1275316","DOI":"10.3389\/fendo.2023.1275316","volume":"14","author":"Y Bruggeman","year":"2023","unstructured":"Bruggeman Y, Martens P-J, Sassi G et al (2023) Footprint of pancreas infiltrating and circulating immune cells throughout type 1 diabetes development. Front Endocrinol 14:1275316. https:\/\/doi.org\/10.3389\/fendo.2023.1275316","journal-title":"Front Endocrinol"},{"issue":"5","key":"6604_CR34","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1073\/pnas.1423769112","volume":"112","author":"AM Magnuson","year":"2015","unstructured":"Magnuson AM, Thurber GM, Kohler RH, Weissleder R, Mathis D, Benoist C (2015) Population dynamics of islet-infiltrating cells in autoimmune diabetes. Proc Natl Acad Sci U S A 112(5):1511\u20131516. https:\/\/doi.org\/10.1073\/pnas.1423769112","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"6604_CR35","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.4049\/jimmunol.0804358","volume":"184","author":"H Brauner","year":"2010","unstructured":"Brauner H, Elemans M, Lemos S et al (2010) Distinct phenotype and function of NK cells in the pancreas of nonobese diabetic mice. J Immunol 184(5):2272\u20132280. https:\/\/doi.org\/10.4049\/jimmunol.0804358","journal-title":"J Immunol"},{"issue":"7","key":"6604_CR36","doi-asserted-by":"publisher","first-page":"836","DOI":"10.2337\/diab.39.7.836","volume":"39","author":"N Nakamura","year":"1990","unstructured":"Nakamura N, Woda BA, Tafuri A et al (1990) Intrinsic cytotoxicity of NK cells to pancreatic islets in vitro. Diabetes 39(7):836\u2013843. https:\/\/doi.org\/10.2337\/diab.39.7.836","journal-title":"Diabetes"},{"issue":"2","key":"6604_CR37","doi-asserted-by":"publisher","first-page":"e0118936","DOI":"10.1371\/journal.pone.0118936","volume":"10","author":"R Yossef","year":"2015","unstructured":"Yossef R, Gur C, Shemesh A et al (2015) Targeting NK cell reactivity by employing antibody to NKp46: implications for type 1 diabetes. PLoS One 10(2):e0118936. https:\/\/doi.org\/10.1371\/journal.pone.0118936","journal-title":"PLoS One"},{"key":"6604_CR38","doi-asserted-by":"publisher","first-page":"722979","DOI":"10.3389\/fimmu.2021.722979","volume":"12","author":"G Gardner","year":"2021","unstructured":"Gardner G, Fraker CA (2021) Natural killer cells as key mediators in type 1 diabetes immunopathology. Front Immunol 12:722979. https:\/\/doi.org\/10.3389\/fimmu.2021.722979","journal-title":"Front Immunol"},{"key":"6604_CR39","doi-asserted-by":"publisher","first-page":"569","DOI":"10.3389\/fendo.2020.00569","volume":"11","author":"M Falcone","year":"2020","unstructured":"Falcone M, Fousteri G (2020) Role of the PD-1\/PD-L1 dyad in the maintenance of pancreatic immune tolerance for prevention of type 1 diabetes. Front Endocrinol 11:569. https:\/\/doi.org\/10.3389\/fendo.2020.00569","journal-title":"Front Endocrinol"},{"key":"6604_CR40","doi-asserted-by":"publisher","first-page":"651","DOI":"10.3389\/fimmu.2015.00651","volume":"6","author":"MN Pham","year":"2015","unstructured":"Pham MN, von Herrath MG, Vela JL (2015) Antigen-specific regulatory T cells and low dose of IL-2 in treatment of type 1 diabetes. Front Immunol 6:651. https:\/\/doi.org\/10.3389\/fimmu.2015.00651","journal-title":"Front Immunol"},{"issue":"12","key":"6604_CR41","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1001\/jama.2023.2064","volume":"329","author":"GP Forlenza","year":"2023","unstructured":"Forlenza GP, McVean J, Beck RW et al (2023) Effect of verapamil on pancreatic beta cell function in newly diagnosed pediatric type 1 diabetes: a randomized clinical trial. JAMA 329(12):990\u2013999. https:\/\/doi.org\/10.1001\/jama.2023.2064","journal-title":"JAMA"},{"issue":"10","key":"6604_CR42","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1007\/s00125-025-06490-8","volume":"68","author":"L Degroote","year":"2025","unstructured":"Degroote L, Martens PJ, Viaene M et al (2025) Verapamil and low-dose anti-mouse thymocyte globulin combination therapy stably reverses recent-onset type 1 diabetes in NOD mice by acting on the beta cell and immune axes. Diabetologia 68(10):2263\u20132276. https:\/\/doi.org\/10.1007\/s00125-025-06490-8","journal-title":"Diabetologia"},{"issue":"1","key":"6604_CR43","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00125-023-06014-2","volume":"67","author":"C Mathieu","year":"2024","unstructured":"Mathieu C, Wiedeman A, Cerosaletti K et al (2024) A first-in-human, open-label Phase 1b and a randomised, double-blind Phase 2a clinical trial in recent-onset type 1 diabetes with AG019 as monotherapy and in combination with teplizumab. Diabetologia 67(1):27\u201341. https:\/\/doi.org\/10.1007\/s00125-023-06014-2","journal-title":"Diabetologia"},{"key":"6604_CR44","doi-asserted-by":"publisher","first-page":"1367514","DOI":"10.3389\/fimmu.2024.1367514","volume":"15","author":"DG Alleva","year":"2024","unstructured":"Alleva DG, Delpero AR, Sathiyaseelan T et al (2024) An antigen-specific immunotherapeutic, AKS-107, deletes insulin-specific B cells and prevents murine autoimmune diabetes. Front Immunol 15:1367514. https:\/\/doi.org\/10.3389\/fimmu.2024.1367514","journal-title":"Front Immunol"},{"issue":"2","key":"6604_CR45","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00125-012-2753-4","volume":"56","author":"KC Herold","year":"2013","unstructured":"Herold KC, Gitelman SE, Willi SM et al (2013) Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia 56(2):391\u2013400. https:\/\/doi.org\/10.1007\/s00125-012-2753-4","journal-title":"Diabetologia"},{"issue":"9","key":"6604_CR46","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41574-023-00853-0","volume":"19","author":"MJ Redondo","year":"2023","unstructured":"Redondo MJ, Morgan NG (2023) Heterogeneity and endotypes in type 1 diabetes mellitus. Nat Rev Endocrinol 19(9):542\u2013554. https:\/\/doi.org\/10.1038\/s41574-023-00853-0","journal-title":"Nat Rev Endocrinol"},{"issue":"4","key":"6604_CR47","doi-asserted-by":"publisher","first-page":"555","DOI":"10.4161\/mabs.24736","volume":"5","author":"F D\u00e9pis","year":"2013","unstructured":"D\u00e9pis F, Hatterer E, Ballet R et al (2013) Characterization of a surrogate murine antibody to model anti-human CD3 therapies. MAbs 5(4):555\u2013564. https:\/\/doi.org\/10.4161\/mabs.24736","journal-title":"MAbs"},{"issue":"2","key":"6604_CR48","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3390\/antib8020028","volume":"8","author":"A Bates","year":"2019","unstructured":"Bates A, Power CA (2019) David vs. Goliath: the structure, function, and clinical prospects of antibody fragments. Antibodies (Basel) 8(2):28. https:\/\/doi.org\/10.3390\/antib8020028","journal-title":"Antibodies (Basel)"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06604-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-025-06604-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06604-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T22:03:03Z","timestamp":1767823383000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-025-06604-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["6604"],"URL":"https:\/\/doi.org\/10.1007\/s00125-025-06604-2","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]},"assertion":[{"value":"28 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We thank J. Laureys from the Leuven Diabetes Lab and S. Tops from PharmAbs for technical assistance. The authors thank the KU Leuven Flow and Mass Cytometry facility. Some of the data were presented as a poster presentation by AW at the 20th meeting of the Immunology of Diabetes Society (IDS) in November 2024 and at the 2nd annual meeting of the young Belgium Immunology Society (yBIS) in May 2025. ESM Fig.\n                      \n                      and the\u00a0graphical abstract were created with BioRender.com.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"All data in this study are available from the corresponding author on reasonable request.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This work was supported by research and infrastructure grants from the Flemish Research Foundation FWO (G.0C63.19N, G.0667.21N, G.0316.25N and I.0018.22N) and KU Leuven (C1 funding C1\/18\/006 and C16\/24\/012, and a small research infrastructure grant KA\/20\/077).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"CM serves or has served on advisory panels for AstraZeneca, Avotres, Boehringer Ingelheim, Eli Lilly and Company, Imcyse, Insulet, Mannkind, Medtronic, Merck Sharp and Dohme Ltd, Novartis, Novo Nordisk, Pfizer, Precigen Actobio, Roche, Sandoz, Sanofi, Vertex Pharmaceuticals and Zealand Pharma. Financial compensation for these activities has been received by KU Leuven.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"All authors have contributed substantially to this study. CG designed the study. AW and CG wrote the first draft of the manuscript. AW, LD, MV and MP assisted in mouse treatment and follow-up. AW, MV and LD performed the spectral flow cytometry staining and AW analysed the data. PL designed the spectral flow cytometry panel and assisted with the unmixing of the raw data and UMAP analysis. NG developed the ADA assay. All authors critically revised the manuscript. CM and CG conceptualised the research goals, acquired major funding and discussed the data. CM and CG are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final version of this manuscript.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}