T Cells and Rejection in Vascularized Composite Allotransplants
Abstract
An estimated 7 million people each year in the United States could benefit from vascularized composite allotransplants (VCAs), such as face and limb transplants, because of traumatic injuries or surgical removal of diseased body parts (for example, body parts that have cancer). Hundreds of American Service members are returning from the armed conflicts in the Middle East with very devastating injuries. These injuries most severely affect unprotected body areas such as the face and limbs, sometimes leading to the loss of multiple limbs. Serious injuries to the face can result in an inability to eat, speak, or communicate, leading to compromised independence, decreased quality of life, and psychological disturbances. Many people who have lost their limbs have difficulty feeding and walking and have chronic pain, leading to a significant reduction in their quality of life. Modern artificial prostheses are very sophisticated and can help perform many important functions of the missing arm(s) and/or leg(s), but prostheses are incapable of providing feeling, and many patients find them difficult to operate, unnatural-looking, or uncomfortable. Recently, it has become possible to treat people with severe facial injuries and limb loss with transplantation of face or limbs from a deceased donor. Face transplants have been successful at restoring sensation and the ability to perform functions such as eating and speaking. Limb transplants have been successful at giving patients new limbs that they can feel and move and that look more natural than prostheses. The adoption of this transformative therapy, however, has been limited, mainly because the patient’s immune system sees the transplanted body parts as foreign and rejects them. Immune rejection causes the transplanted parts to become damaged, and if not treated promptly, can lead to the loss of the transplants. Acute rejection episodes occur more frequently in face and limb transplants, compared to other internal organ transplants such as kidney transplants. Researchers do not know exactly why this is the case. It is critical to understand the mechanisms that underlie this difference because it may lead to development of anti-rejection therapies that are specifically effective for transplants such as face and limbs. Our team has performed the most face transplants at a single center in the world and has extensive expertise in managing patients who have had face and limb transplants. In this proposed study, we will take advantage of the recent breakthroughs in genomic techniques to study immune rejection in face and limb transplants. Previous studies have suggested that skin contains many T cells and, therefore, transplantation of body parts that contain the skin (such as face or limb transplants) can transfer a significant number of T cells from the deceased donor. Although we know T cells can cause acute rejection, the current thinking is that rejection is exclusively driven by the T cells from the recipient. This proposal challenges this current paradigm and will investigate the role of donor T cells in rejection. If we find that donor T cells contribute to rejection, their removal before transplantation will be developed as an entirely new anti-rejection therapy. Second, we will test blood samples from the recipients to investigate whether the particular T cell clones that drive rejection within the transplant can also be detected in their blood. It is important to find out whether this is the case because it will allow clinicians to monitor these specific T cell clones in blood to monitor the health of transplants. Because the T cell clones that cause rejection in each recipient are unique, this method will allow clinicians to monitor rejection in a precise and personalized manner and identify the patients who are at risk of rejection to treat them early. This proactive approach will spare patients the complications of over-immunosuppression and, at th
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810784
Entities
People
- Rachael Clark
Organizations
- United States Army