Joren Christian Madsen, D.PHIL., M.D.
|Title||Professor of Surgery|
|Institution||Massachusetts General Hospital|
|Address||Massachusetts General Hospital|
Surgery, Bulfinch 119
55 Fruit St
Boston MA 02114
Available: 12/01/12, Expires: 06/01/14
When hearts are transplanted into miniature swine or nonhuman primates treated with a tolerance induction protocol, they all reject. In contrast, when hearts are co-transplanted with kidneys from the same donors, the hearts all accept permanently. The explanation and implications of this finding for the induction of tolerance to human heart transplant recipients are the focus of this proposal.
The mechanism by which a heart is protected from both acute and chronic rejection by the tolerant state induced following a kidney allograft is unknown. Our previous work shows that based on our previous work, we hypothesize that host thymus-derived regulatory T cells, generated by cells or antigens in the donor kidney, are responsible for the induction of tolerance to cardiac allografts in heart/kidney recipients. The corollary is that regulatory T cells are present in tolerant recipients bearing long-term cardiac allografts but are not present in chronically immunosuppressed recipients bearing long-term cardiac allografts. We will test these hypotheses by performing experiments with four specific aims.
Aim 1. Determine the in vitro characteristics of regulatory T cells from tolerant heart/kidney recipients.
Aim 2. Determine the role of regulatory T cells in the induction and maintenance phase of tolerance in heart/kidney recipients.
Aim 3. Determine how a state of tolerance modifies the effects of intragraft cytokine excess in heart/kidney recipients.
Aim 4. Compare the in vitro parameters of transplant immunity in animals bearing allogeneic heart transplants prolonged by tolerance induction vs. chronic immunosuppression.
The student will be intimately involved in all aspects of these studies including experimental design, large animal surgery, in vitro assays, data analysis and manuscript preparation.
The Role of the Renal Tubular Epithelial Cell in Kidney-Induced Cardiac Allograft Tolerance
Summer, 06/11/12 - 08/17/12
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