B Lymphocyte-Induced Maturation Protein-1 Promotes Allograft Survival via Modulation of T Cell Development.
1VCA
PRS Dept., CGMH, Taoyuan, Taiwan
2Department of Microbiology and Immunology, NDMC, Taipei, Taiwan
3Division of Surgery and Interventional Science, University College London, London, United Kingdom
4College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Meeting: 2016 American Transplant Congress
Abstract number: B25
Keywords: Alloantigens, Allorecognition, Graft survival, Inflammation
Session Information
Session Name: Poster Session B: Allograft Rejection, Tolerance, and Xenotransplantation
Session Type: Poster Session
Date: Sunday, June 12, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
*Equal contribution
Purpose
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.
Methods/ Results
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.
Conclusion
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 May 9, 2025.« Back to 2016 American Transplant Congress