Background: Foxp3+Tregs have an essential role in allograft tolerance. Aim: To evaluate Foxp3+Tregs in the spontaneous tolerance of mouse renal allografts. Methods: A standard mouse renal transplant tolerance model DBA/2(H-2d) to C57BL/6(H-2b) was used. The recipients included C57BL/6, Foxp3RFP, Foxp3GFP and DEREG mice (all on C57BL/6 background), with a host nephrectomy was performed. DEREG mice were used for depletion of Tregs. DT was given to DEREG mice for 3 days prior to transplant. Foxp3RFP, Foxp3GFP allowed tracking of Tregs. Renal allografts were harvested from at day 7, 14 and ³69 post transplantation(PTX). Allograft I-Tregs(CD4+GFP+) were sorted by FACS and expression of cytokines, Blimp-1 and CXCR3 assessed. I-Tregs of day 14 PTX were adoptively transferred into Rag-/- mice to assess dominant tolerance. Results: Treg-depleted DEREG mice, rejected DBA/2 renal allografts (n=8) with a median survival time (MST) of 6.5 days. In contrast C57BL/6 background mice (n=39) showed long-term tolerance with a MST>100 days (p<0.0001) for DBA renal allografts. Tolerant renal allografts at day 7 and >100 days had localized interstitial infiltrates of mononuclear cells. GFP+ Tregs were found in tolerant allografts at day 7 and >100 PTX but not in rejecting allografts. The proportion of Tregs increased the renal allograft at day 7 and 14 PTX (p<0.05). Tregs were highest in the draining LN (DLN) compared to PB and control LN at day 7and >84 PTx in Foxp3GFP mice (p<0.05). Allograft I-Tregs express elevated levels of TGF-Β, IL-10, Blimp-1, and CXCR3. Adoptively transferring I-Tregs into Rag-/- mice which were subsequently transplanted with DBA/2 skin grafts showed skin graft survival was greater than 100 days and remained intact following challenge with non-Tregs (CD4+GFP–). Conclusion: Renal allografts require Tregs to develop tolerance in this model. This is associated with increased Blimp-1, and CXCR3 in allograft I-Tregs that can transfer dominant tolerance.
To cite this abstract in AMA style:Hu M, Wang C, Zhang G, Saito M, Wang Y, Fernandez M, Qian Y, Wang Y, Sawyer A, Hawthorne W, Jones C, Sparwasser T, Bishop A, Sharland A, O'Connell P, Alexander S. Graft Infiltrating Foxp3 Tregs in Spontaneously Tolerant Renal A Allografts Express High Levels of CXCR3 and BLIMP-1 [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/graft-infiltrating-foxp3-tregs-in-spontaneously-tolerant-renal-a-allografts-express-high-levels-of-cxcr3-and-blimp-1/. Accessed November 19, 2019.
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