1 Low Dose IL-2 Combined with Rapamycin Led to an Expansion of CD4 + CD25 + FOXP3 + Tregs and Prolonged Human Islet-allograft Survival in Humanized Mice Running title: IL-2 and Rapamycin Therapy in Islet Transplant Min Hu 1,2 , Wayne J Hawthorne 1 , Leigh Nicholson 1 , Heather Burns 1 , Yi Wen Qian 1 , David Liuwantara 1 , Elvira Jimenez Vera 1 , Yi Vee Chew 1 , Lindy Williams 1 , Shounan Yi 1 , Karen Keung 1 , Debbie Watson 3 , Natasha Rogers 1 , Stephen I Alexander 4 and Philip J O’Connell 1,2 1 Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Sydney, Australia, 2 Westmead Clinical Schools, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia, 3 Molecular Horizons and School of Chemistry and Molecular Bioscience, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia, 4 Centre for Kidney Research, Children's Hospital at Westmead, Sydney, Australia Address correspondence: Min Hu, MBBS, MMed, PhD and Philip J O’Connell, MD, PhD, Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, Westmead, New South Wales 2145, Australia. Telephone: 61-2-86273049 and 62-2-86273501 E-mails: min.hu@sydney.edu.au and Philip.oconnell@sydney.edu.au Word count: 4000 words; Figure count: 8 Figures. Online supplemental material: Two supplementary tables and Human Islet checklist. Supporting data: 5 supplemental figures. Key words: Human islet-allografts; Regulatory T cells; Combination of IL-2 and rapamycin therapy; Human allograft rejection; Humanized Mouse Model; Page 2 of 64 Diabetes Diabetes Publish Ahead of Print, published online May 7, 2020