Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Background: Allograft survival depends on the balance of effector T cells (Teff) and regulatory T cells (Tregs). Previous study suggested that the balance is controlled by HIF-1α. In this study, we investigated the role of HIF-1α-deficient CD4 T-cell in promoting acceptance of vascularized composite allografts.
Methods: Forty osteomyocutaneous allografts from Balb/c were transplanted to wild type (WT) and HIF-1αfl/flCD4Cre C57BL/6 mice. Animals received combined costimulation blockade (1 mg anti-CD154 at POD 0, 0.5 mg CTLA4Ig at POD 2) with or without rapamycin (3mg/kg/day for 7 days then every other day for 3 weeks). Allograft survival, ratio of Tregs/Teff cells in the periphery and allograft were assessed.
Results:Twelve of 15 WT recipients under costimulation blockade and 1-month rapamycin achieved long-term allograft survival (>120 days). In the tolerant animals, ratio of Tregs/Th1 cells and Tregs/Th17 cells in periphery at POD 30 and in allograft were greater than those in rejected animals. In MLR study, conditional HIF-1α deficiency in CD4 resulted CD4 T-cell hyporesponsiveness. HIF-1αfl/flCD4Cre mice generated greater FoxP3+ Tregs and less CD4+IL17+ cells than WT in response to allografts. Without the use of rapamycin, improved allograft survival ratewas achieved in HIF-1αfl/flCD4Cre mice compared to WT mice (> 120 vs 36.5 days). But adoptively transferred Th17 cells at POD 2 in HIF-1α fl/flCD4Cre recipients disrupted the allograft survival. Animals with long-term allograft survival showed donor-specific T cell hypo responsiveness.
Conclusion: Loss of HIF-1α in CD4 T cells improves allograft survival in the absence of long-term immunosuppressant drugs. Targeting potential mechanisms involved in the differentiation of CD4 T cells may play an important role in improving allograft survival.
CITATION INFORMATION: Lin C-.H., Anggelia M., Yang H., Chuang W., Cheng H., Wei F-.C., Brandacher G. Loss of HIF-1α in CD4 T Cell Improve Outcome of Mouse Vascularized Osteomyocutaneous Allotransplantation under Costimulation Blockade Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Lin C-H, Anggelia M, Yang H, Chuang W, Cheng H, Wei F-C, Brandacher G. Loss of HIF-1α in CD4 T Cell Improve Outcome of Mouse Vascularized Osteomyocutaneous Allotransplantation under Costimulation Blockade [abstract]. https://atcmeetingabstracts.com/abstract/loss-of-hif-1-in-cd4-t-cell-improve-outcome-of-mouse-vascularized-osteomyocutaneous-allotransplantation-under-costimulation-blockade/. Accessed October 31, 2020.
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