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Your search keyword '"Yi, Shounan"' showing total 7 results
Start Over Author "Yi, Shounan" Publisher american diabetes association
7 results on '"Yi, Shounan"'

1. Adoptive transfer with in vitro expanded human regulatory T cells protects against porcine islet xenograft rejection via interleukin-10 in humanized mice

Author

Yi, Shounan, Ji, Ming, Wu, Jingjing, Ma, Xiaoqian, Phillips, Peta, Hawthorne, Wayne J., and O'Connell, Philip J.

Subjects
T cells -- Physiological aspects -- Genetic aspects -- Research, Interleukin-10 -- Physiological aspects -- Genetic aspects -- Research, Graft rejection -- Development and progression -- Genetic aspects -- Prevention, Health
Abstract

T cell-mediated rejection remains a barrier to the clinical application of islet xenotransplantation. Regulatory T cells (Treg) regulate immune responses by suppressing effector T cells. This study aimed to determine the ability of human Treg to prevent islet xenograft rejection and the mechanism(s) involved. Neonatal porcine islet transplanted NOD-SCID IL2r[γ.sup.-/-] mice received human peripheral blood mononuclear cells (PBMC) with in vitro expanded autologous Treg in the absence or presence of anti-human interleukin-10 (IL-10) monoclonal antibody. In addition, human PBMC-reconstituted recipient mice received recombinant human IL-10 (rhIL-10). Adoptive transfer with expanded autologous Treg prevented islet xenograft rejection in human PBMC-reconstituted mice by inhibiting graft infiltration of effector cells and their function. Neutralization of human IL-10 shortened xenograft survival in mice receiving human PBMC and Treg. In addition, rhIL-10 treatment led to prolonged xenograft survival in human PBMC-reconstituted mice. This study demonstrates the ability of human Treg to prevent T-cell effector function and the importance of IL-10 in this response. In vitro Treg expansion was a simple and effective strategy for generating autologous Treg and highlighted a potential adoptive Treg cell therapy to suppress antigraft T-cell responses and reduce the requirement for immunosuppression in islet xenotransplantation. Diabetes 61:1180-1191, 2012, Pancreatic islet transplantation as a treatment for type 1 diabetes received a major impetus with the development of the Edmonton protocol and recent clinical trials demonstrating long-term insulin independence out [...]

Published
2012
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2. 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

Author

Hu, Min, primary, Hawthorne, Wayne J., additional, Nicholson, Leigh, additional, Burns, Heather, additional, Qian, Yi Wen, additional, Liuwantara, David, additional, Jimenez Vera, Elvira, additional, Chew, Yi Vee, additional, Williams, Lindy, additional, Yi, Shounan, additional, Keung, Karen, additional, Watson, Debbie, additional, Rogers, Natasha, additional, Alexander, Stephen I., additional, and O’Connell, Philip J., additional

Published
2020
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3. 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

Author

Admin, Ada, primary, Hu, Min, primary, Hawthorne, Wayne J, primary, Nicholson, Leigh, primary, Burns, Heather, primary, Qian, Yi Wen, primary, Liuwantara, David, primary, Vera, Elvira Jimenez, primary, Chew, Yi Vee, primary, Williams, Lindy, primary, Yi, Shounan, primary, Keung, Karen, primary, Watson, Debbie, primary, Rogers, Natasha, primary, Alexander, Stephen I, primary, and O’Connell, Philip J, primary

Published
2020
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4. 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.

Author

Hu, Min, Hawthorne, Wayne J., Nicholson, Leigh, Burns, Heather, Qian, Yi Wen, Liuwantara, David, Jimenez Vera, Elvira, Chew, Yi Vee, Williams, Lindy, Yi, Shounan, Keung, Karen, Watson, Debbie, Rogers, Natasha, Alexander, Stephen I., and O'Connell, Philip J.

Subjects
SUPPRESSOR cells, INTERLEUKIN-2, RAPAMYCIN, ISLANDS of Langerhans, TYPE 1 diabetes, PROTEIN metabolism, ANIMAL experimentation, CELL culture, COMPARATIVE studies, FLOW cytometry, GRAFT rejection, HOMOGRAFTS, RESEARCH methodology, MEDICAL cooperation, MICE, RESEARCH, T cells, EVALUATION research, PHARMACODYNAMICS
Abstract

Islet transplantation is an emerging therapy for type 1 diabetes and hypoglycemic unawareness. However, a key challenge for islet transplantation is cellular rejection and the requirement for long-term immunosuppression. In this study, we established a diabetic humanized NOD-scidIL2Rγnull (NSG) mouse model of T-cell-mediated human islet allograft rejection and developed a therapeutic regimen of low-dose recombinant human interleukin-2 (IL-2) combined with low-dose rapamycin to prolong graft survival. NSG mice that had received renal subcapsular human islet allografts and were transfused with 1 × 107 of human spleen mononuclear cells reconstituted human CD45+ cells that were predominantly CD3+ T cells and rejected their grafts with a median survival time of 27 days. IL-2 alone (0.3 × 106 IU/m2 or 1 × 106 IU/m2) or rapamycin alone (0.5-1 mg/kg) for 3 weeks did not prolong survival. However, the combination of rapamycin with IL-2 for 3 weeks significantly prolonged human islet allograft survival. Graft survival was associated with expansion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) and enhanced transforming growth factor-β production by CD4+ T cells. CD8+ T cells showed reduced interferon-γ production and reduced expression of perforin-1. The combination of IL-2 and rapamycin has the potential to inhibit human islet allograft rejection by expanding CD4+FOXP3+ Tregs in vivo and suppressing effector cell function and could be the basis of effective tolerance-based regimens. [ABSTRACT FROM AUTHOR]

Published
2020
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7. 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.

Author

Hu M, Hawthorne WJ, Nicholson L, Burns H, Qian YW, Liuwantara D, Jimenez Vera E, Chew YV, Williams L, Yi S, Keung K, Watson D, Rogers N, Alexander SI, and O'Connell PJ

Subjects
Allografts, Animals, CD4-Positive T-Lymphocytes drug effects, Cells, Cultured, Flow Cytometry, Graft Rejection, Humans, Mice, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory metabolism, CD4-Positive T-Lymphocytes metabolism, Forkhead Transcription Factors metabolism, Interleukin-2 pharmacology, Interleukin-2 Receptor alpha Subunit metabolism, Sirolimus pharmacology
Abstract

Islet transplantation is an emerging therapy for type 1 diabetes and hypoglycemic unawareness. However, a key challenge for islet transplantation is cellular rejection and the requirement for long-term immunosuppression. In this study, we established a diabetic humanized NOD-scidIL2Rγ null (NSG) mouse model of T-cell-mediated human islet allograft rejection and developed a therapeutic regimen of low-dose recombinant human interleukin-2 (IL-2) combined with low-dose rapamycin to prolong graft survival. NSG mice that had received renal subcapsular human islet allografts and were transfused with 1 × 10 7 of human spleen mononuclear cells reconstituted human CD45 + cells that were predominantly CD3 + T cells and rejected their grafts with a median survival time of 27 days. IL-2 alone (0.3 × 10 6 IU/m 2 or 1 × 10 6 IU/m 2 ) or rapamycin alone (0.5-1 mg/kg) for 3 weeks did not prolong survival. However, the combination of rapamycin with IL-2 for 3 weeks significantly prolonged human islet allograft survival. Graft survival was associated with expansion of CD4 + CD25 + FOXP3 + regulatory T cells (Tregs) and enhanced transforming growth factor-β production by CD4 + T cells. CD8 + T cells showed reduced interferon-γ production and reduced expression of perforin-1. The combination of IL-2 and rapamycin has the potential to inhibit human islet allograft rejection by expanding CD4 + FOXP3 + Tregs in vivo and suppressing effector cell function and could be the basis of effective tolerance-based regimens., (© 2020 by the American Diabetes Association.)

Published
2020
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