CL22 protection of islet allografts in diabetes

Joel Montané Mogas, Loraine Bischoff, Galina Soukhatcheva, Rusung Tan, C. Bruce Verchere

Research output: Conference paperContribution

Abstract

CD4+ CD25+ T regulatory (Treg) cells prevent spontaneous development of autoimmune diabetes and may delay islet allograft rejection. Tumour cells attract Treg cells to foster immune privilege by producing the chemokine CCL22, which promotes trafficking of Treg cells to the tumour. Therefore, manipulating Treg migration with CCL22 may provide a means of preventing islet transplant rejection in autoimmune diabetes. To drive islet-specific expression of CCL22 we created an adenovirus (Ad-CCL22) in which a mouse CCL22 cDNA is expressed downstream of the CMV promoter. Isolated islets transduced with Ad-CCL22 (10 MOI) produced and secreted high levels of CCL22 in vitro whereas CCL22 production by non-transduced islets was undetectable. To determine whether CCL22 expression prevents islet allograft rejection, donor Balb/c islets were isolated and transduced overnight with Ad-CCL22 (n= 6) or Ad-lacZ (n= 5). Islets (300 per recipient) were then transplanted into the left renal subcapsular space of age-matched female C57/BL6 diabetic recipients. By 5 weeks post-transplant, only 1 of 7 CCL22-expressing islet grafts had been rejected whereas 4 of 5 Ad-LacZ-transduced grafts were rejected. Induced expression of CCL22 by transplanted islets thus delays islet allograft rejection. Manipulation of Tregs cells by CCL-22 in transplanted islets may be a novel therapeutic strategy for diabetes.
Translated title of the contributionCL22 protection of islet allografts in diabetes.
Original languageEnglish
Publication statusPublished - 1 Jan 2009
Event96 Annual Meeting of The American Association of Immunologists: Immunology 2009 - Seattle, United States
Duration: 8 May 200912 May 2009
Conference number: 96

Conference

Conference96 Annual Meeting of The American Association of Immunologists
Country/TerritoryUnited States
CitySeattle
Period8/05/0912/05/09

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