Background: B cell activation factor of the TNF family (BAFF) is considered to function as a proinflammatory cytokine. BAFF is crucial for B cell development and survival. We and others have shown a role for BAFF in expanding Tregs in vivo in both skin and islet transplant models using the BAFF-transgenic (-Tg) mouse. However the role of BAFF in vascularized organ transplants such as cardiac transplants has not been evaluated.
Methods: Three groups of mice received heterotopic cardiac transplants. The Group 1 (syngeneic controls) [from C57Bl/6 (H-2b) to C57Bl/6 (H-2b): n=6], the group 2 allogeneic controls [from BALB/c (H-2d) to C57Bl/6 (H-2b): n=7], and the group 3 allogeneic into the BAFF-Tg mice [from BALB/c (H-2d) to BAFF-Tg (H-2b): n=6]. We assessed the graft survival, histological, and immune phenotyping including Tregs by flow cytometry between the groups.
Results: WT mice rapidly rejected allogeneic cardiac allografts [mean survival time (MST) = 8 days] while the BAFF-Tg mice exhibited a significant delay in the rejection (MST = 12 days). The BAFF-Tg mice have increased peripheral Tregs and increased Tregs were found in the peripheral blood and in the graft in the BAFF-Tg mice. Treg depletion with PC61 led to more rapid rejection (MST = 8 days). Foxp3, IL-10, and TGF-beta mRNA expression were increased in both cardiac allograft and spleen of the BAFF-Tg mice compared to the allogeneic controls and Treg-depleted BAFF-Tg mice. The BAFF-Tg mice demonstrated a decrease in serum pro-inflammatory cytokines and an increase in IL-10.
Conclusions: BAFF protects against cardiac allograft rejection and this is a function of Treg expansion.
To cite this abstract in AMA style:Saito M, Zhang G, Wang Y, Hu M, Walters S, Zhou J, Sawyer A, Chapman J, Grey S, Alexander S. Prolonged Cardiac Allograft Survival Due to Treg Expansion in Recipient BAFF-Tg Mice [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/prolonged-cardiac-allograft-survival-due-to-treg-expansion-in-recipient-baff-tg-mice/. Accessed October 28, 2020.
« Back to 2013 American Transplant Congress