<< Back to the abstract archive
The regulatory function of CD4-CD8- Double Negative T cells enhances mouse osteomyocutaneous flap survival
Ng, Timothy W.; Lin, Cheng-Hung; Zhang, Dong; Pulikkottil, Benson J.; Lee, W.P. Andrew; and Zheng, Xinxiao
University of Pittsburgh Medical Center
Surgical Translational Research Training Program
2010-03-31
Presenter: Timothy W. Ng
Affidavit:
Director Name:
Author Category: Resident/Fellow
Presentation Category: Basic Science Research
Abstract Category: Hand
BACKGROUND:
The loss of a face or limb is a devastating defect that is difficult to address with conventional methods. However, composite tissue allotransplantation (CTA), heterogenous grafts containing bone, muscle, nerve, and skin, can restore appearance, function and dignity to the patient. But, CTA requires immunosuppressive drugs, which can have severe side effects.
Immunoregulatory cells may wean patients off immunosuppressants. In our previous report, peripheral CD4+ T cells were converted into CD4-CD8- double negative (DN) T cells, which regulate allo- and auto- immune responses. DN T cells therapy alone significantly prolongs islet allograft survival.
METHODS:
In this study, we tested the combination of DN T cells and a low dose immunosuppressant, rapamycin, in a complete MHC mismatched, mouse skin transplant model. Moreover, the treatment was also tested in a murine, osteomyocutaenous thigh flap CTA model.
RESULTS:
Low dose rapamycin and DN cells have a synergistic effect on decreasing both CD4 and CD8 T cell proliferation and increasing apoptosis. Moreover, the combination treatment significantly extended skin graft survival (mean survival time 28 days). Interestingly, the addition of lymphoablative conditioning or cytokine immunomodulation to Rapamycin+DN extended skin graft survival beyond 60 days. Early results from osteomyocutaenous flaps resemble the skin graft data.
SUMMARY:
- Using a novel cellular induction method, highly potent, antigen specific, immunosuppressive DN cells were produced in vitro
- DN cells prevent acute rejection in skin grafts
- Our novel surgical model is the first application of DN T cells in composite tissue allotransplantation
