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CCL22 Prevents Rejection of Mouse Islet Allografts and Induces Donor-Specific Tolerance
- Source :
- Cell Transplantation, Vol 24 (2015)
- Publication Year :
- 2015
- Publisher :
- SAGE Publishing, 2015.
-
Abstract
- Manipulation of regulatory T cell (Treg) migration by islet expression of the chemokine CCL22 prevents diabetes in NOD mice and delays recurrent autoimmunity in syngeneic islet transplants. We sought to determine whether attracting Tregs with CCL22 also prevents islet allograft rejection. Isolated Bl/6 mouse islets were transduced overnight with adenovirus expressing CCL22 (Ad-CCL22) downstream of the CMV promoter. Islets were transplanted under the renal capsule of Balb/c recipients made diabetic by streptozotocin. To assess immunologic tolerance, graft-bearing kidneys from recipients of CCL22-expressing islet grafts were removed, and mice received a second transplant of naive islets from the same donor strain or third-party islets into the contralateral kidney. Adenoviral expression of CCL22 conferred prolonged protection of islet allografts in MHC-mismatched, diabetic recipients, maintaining normoglycemia in 75% of recipients for at least 80 days. Increased frequency of Treg cells was observed in islet grafts transduced with Ad-CCL22 compared with untreated grafts. Normoglycemic recipients of CCL22-expressing islet grafts showed complete absence of antidonor antibodies and no lymphocyte proliferation after exposure to donor splenocytes. After removal of the primary graft at day 80, mice that received a second transplant with untreated islets from the same donor strain did not reject the grafts, suggesting the development of tolerance. Expression of CCL22 recruits Treg cells to transplanted islets, prevents activation of alloreactive T-cells and islet allograft failure and induces alloantigen-specific tolerance. Manipulation of Treg cells by CCL22 in transplanted islets may be a novel therapeutic strategy for diabetes.
- Subjects :
- Isoantigens
endocrine system
endocrine system diseases
Regulatory T cell
Islets of Langerhans Transplantation
Biomedical Engineering
lcsh:Medicine
Lymphocyte proliferation
Biology
T-Lymphocytes, Regulatory
Diabetes Mellitus, Experimental
Immune tolerance
Mice
Renal capsule
Immune Tolerance
medicine
Animals
Transplantation, Homologous
NOD mice
Chemokine CCL22
Transplantation
geography
geography.geographical_feature_category
Graft Survival
lcsh:R
Cell Biology
Allografts
Streptozotocin
Islet
medicine.anatomical_structure
surgical procedures, operative
Immunology
Transplantation Tolerance
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 15553892 and 09636897
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Cell Transplantation
- Accession number :
- edsair.doi.dedup.....37a094df0d853572c6f7811929830002