Date: Monday, May 4, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 2:51pm-3:03pm
Location: Room 121-C
Background: We have previously reported successful induction of solid organ allograft tolerance in nonhuman primates (NHP) via a mixed chimerism approach. Since these recipients achieved allograft tolerance with transient chimerism, peripheral mechanisms are considered playing a major role in the maintenance of tolerance. In this study, we evaluated the role of regulatory T cells (Treg) in NHP that achieved long-term allograft survival without immunosuppression (IS).
Method: All recipients underwent combined solid organ (kidney, heart or lung) and donor bone marrow transplantation. Seven allograft recipients [kidney (5) and lung (2)] that achieved long-term (>300 days) allograft survival (LTS) without IS were investigated. Six recipients [heart (4) and kidney (2)] that received the same regimen but acutely rejected their allografts were evaluated as controls (AR). T-cell responses were evaluated by mixed lymphocyte responses (MLR) with CFSE/CD4, CD8 and Foxp3 staining.
Results: While donor specific CD8+ T cell non-responsiveness was observed in LTS (but not in AR), significant anti-donor CD4+ T cell proliferation was observed in both LTS and AR. However, among these proliferated CD4+ cells, significantly higher Foxp3+ cell proliferation was observed in LTS, comparing with those in AR (P<0.01). The FoxP3+ cell proliferation in LTS was donor specific, as significantly higher Foxp3+ cell proliferation was observed in MLR against the donor than those against the third party stimulators (P<0.01)(Fig.1). Interestingly, these proliferated Tregs appeared to be converted from Non-Tregs, as significant proliferation of Foxp3+ cells was observed only after anti-donor MLR with sorted CD4+CD25- (non-Tregs), but not with sorted Treg (CD4+CD25high) cells (Fig. 2). Finally, suppressive function of these proliferated cells after MLR was confirmed by inhibition of T cell activation.
Conclusion: Donor specific expansion of Tregs was associated with long-term allograft tolerance induced after transient mixed chimerism.
To cite this abstract in AMA style:Hotta K, Aoyama A, Ohura T, Tonsho M, Yamada Y, Allan J, Madsen J, Cosimi B, Benichou G, Kawai T. Donor Specific Expansion of Regulatory T-Cells Was Associated With Allograft Tolerance Induced By Transient Mixed Chimerism in Nonhuman Primates [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-specific-expansion-of-regulatory-t-cells-was-associated-with-allograft-tolerance-induced-by-transient-mixed-chimerism-in-nonhuman-primates/. Accessed May 20, 2019.
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