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-2^b) to C57Bl/6 (H-2^b): n=6], the group 2 allogeneic controls [from BALB/c (H-2^d) to C57Bl/6 (H-2^b): n=7], and the group 3 allogeneic into the BAFF-Tg mice [from BALB/c (H-2^d) to BAFF-Tg (H-2^b): 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.

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