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


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Abstract

Background: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.Methods:This study is the first to investigate transplanted skin allograft survival using transgenic (Tg) mice with T cell overexpression of Blimp-1.Results: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.Discussion:As such, allograft survival was made possible due to Th1 suppression and Treg amplification with the creation of an ‘allograft protective microenvironment’.HIGHLIGHTSBlimp-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.

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