Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 13, Issue 11, Pages 2819-2830Publisher
WILEY
DOI: 10.1111/ajt.12445
Keywords
Depletion of Foxp3(+) Tregs; DEREG mice; donor alloantigen-specific tolerance; kidney allograft infiltrating Foxp3(+) Tregs; spontaneous kidney allograft tolerance
Categories
Funding
- National Health and Medical Research Council of Australia (NHMRC) [1029205, 1029601, 512246]
- NHMRC Training Fellowship [APP1013185]
Ask authors/readers for more resources
Foxp3(+) regulatory T cells (Tregs) have an essential role in immune and allograft tolerance. However, in both kidney and liver transplantation in humans, FOXP3(+) Tregs have been associated with clinical rejection. Therefore, the role and function of graft infiltrating Tregs have been of great interest. In the studies outlined, we demonstrated that Foxp3(+) Tregs were expanded in tolerant kidney allografts and in draining lymph nodes in the DBA/2 (H-2(d)) to C57BL/6 (H-2(b)) mouse spontaneous kidney allograft tolerance model. Kidney allograft tolerance was abrogated after deletion of Foxp3(+) Tregs in DEpletion of REGulatory T cells (DEREG) mice. Kidney allograft infiltrating Foxp3(+) Tregs (K-Tregs) expressed elevated levels of TGF-, IL-10, interferon gamma (IFN-), the transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) and chemokine receptor 3 (Cxcr3). These K-Tregs had the capacity to transfer dominant tolerance and demonstrate donor alloantigen-specific tolerance to skin allografts. This study demonstrated the crucial role, potency and specificity of graft infiltrating Foxp3(+) Tregs in the maintenance of spontaneously induced kidney allograft tolerance. The authors study regulatory T cells from tolerant kidney allografts and demonstrate that these cells exhibit potent and specific suppression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available