Date: Sunday, June 12, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Vascularized composite allotransplantation (VCA) is a promising new field in plastic surgery. Skin is known to be the most immunogenic component of a composite tissue and therefore is the primary target of T cell-mediated rejection. B lymphocyte-induced maturation protein-1 (Blimp-1) transcription factor, a regulator for the terminal differentiation of B cells into plasma cells, has never been investigated for its potential role in T cell-mediated tolerance after skin transplantation. We used transgenic (Tg) C57BL/6 mice, with overexpression of Blimp-1 in T cells, to directly study its potential role in promoting allograft survival.
Skin grafts from the tails of BALB/c mice were transplanted to Tg(-) or Tg(+) mice.
Tg(-) mice consistently demonstrated rejection around postoperative day 7 whereas Tg(+) mice significantly prolonged skin allograft survival without any immunosuppressive regimen. This correlated with histological findings of a lesser degree of skin allograft lymphocytic infiltration in Tg(+) mice.
The macroscopic findings were due to a hyporesponsive alloimmune response in Tg(+) compared to Tg(-) mice on mixed lymphocyte proliferation assay.
Systemic changes represented by peripheral blood from Tg(+) mice showed remarkably decreased proinflammatory IFN-γ producing Th1 cells and increased anti-inflammatory regulatory T cells (Treg) after skin transplantation when analysed using flow cytometry.
Peri-graft proinflammatory versus anti-inflammatory cells were reduced which was reflected by a decreased ratio of Th1 to Treg cells in Tg(+) mice using quantitative qPCR analysis. This is further evidenced by a significant decrease in peri-graft Th1 associated cytokines such as IFN-γ and IL-12. Cytotoxic tissue destroying enzymes such as granzyme B and perforin were significantly reduced locally as well in Tg(+) mice.
The evidence presented conclusively proves that overexpression of Blimp-1 in T cells is key in the orchestration of an anti-inflammatory cell-cytokine composition, both systemically and locally, which in turn results in the promotion of skin allograft survival through the creation of a 'graft protective microenvironment'.
CITATION INFORMATION: Wang A, Loh C, Chen S.-J, Lin C.-H, Sytwu H.-K, Chuang S.-H, Wei F.-C. B Lymphocyte-Induced Maturation Protein-1 Promotes Allograft Survival via Modulation of T Cell Development. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Wang A, Loh C, Chen S-J, Lin C-H, Sytwu H-K, Chuang S-H, Wei F-C. B Lymphocyte-Induced Maturation Protein-1 Promotes Allograft Survival via Modulation of T Cell Development. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/b-lymphocyte-induced-maturation-protein-1-promotes-allograft-survival-via-modulation-of-t-cell-development/. Accessed December 14, 2019.
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