Blimp-1 prolongs allograft survival without regimen via influencing T cell development in favor of regulatory T cells while suppressing Th1

• Published in: Molecular immunology 2018-07, Vol.99, p.53-65
• Main Authors: Wang, Aline Yen Ling, Loh, Charles Yuen Yung, Chen, Shyi-Jou, Kao, Huang-Kai, Lin, Cheng-Hung, Chuang, Sheng-Hao, Lee, Chin-Ming, Sytwu, Huey-Kang, Wei, Fu-Chan
• Format: Article
• Language: English
• Subjects: Allograft tolerance; B lymphocyte-induced maturation protein; T cells
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2018.04.004

•Blimp-1 is expressed in multiple cell lineages and in particular, T cells.•It is the first study for allograft survival in Blimp-1 T-cell transgenic mice.•Blimp-1 T-cells modulate skin allograft survival without immunosuppression.•T-bet reduction and FoxP3 increment occur in Blimp-1 T-cells.•Blimp-1 creates a favorable condition via Th1 suppression and Treg amplification. B lymphocyte-induced maturation protein 1 (Blimp-1) transcription factor is expressed in multiple cell lineages and in particular, T cells. However, the role of Blimp-1 in T cell-mediated allograft tolerance is still unknown. This study is the first to investigate transplanted skin allograft survival using transgenic (Tg) mice with T cell overexpression of Blimp-1. Without any immunosuppression, fully MHC-mismatched skin allografts on Tg(+) mice had a significantly prolonged survival rate and partial tolerance at 90 days. Allograft lymphocytic infiltration was decreased in Tg(+) mice and a dampened donor-stimulated alloimmune response was seen. An absolute cell number ratio of inflammatory Th1 and Th17 cells against anti-inflammatory regulatory T (Treg) and IL-10-producing T cells, as well as cytolytic proteins, were significantly decreased in lymphoid organs and allograft. Blimp-1 transgenic T cells displayed an increased Treg differentiation capability and enhanced suppression of T cell proliferation. Overexpression of Blimp-1 in T cells promoted the formation of an anti-inflammatory cell-cytokine composition, both systemically and locally via transcription factor modulation such as T-bet downregulation and FoxP3 upregulation. As such, allograft survival was made possible due to Th1 suppression and Treg amplification with the creation of an ‘allograft protective microenvironment’.