Research Group
- Dr Mark Howard Siegelman, Principal Investigator
- Dr Pila Estess, Clinical Research Coordinator
- Dr Christopher Lu, Collaborator
- Dr Peter Stastny, Collaborator
- Dr Ingemar Davidson, Collaborator
- Dr Marlon Levy, Collaborator
Location
- University of Texas Southwestern Medical Center, Dallas, USA
Title
- Use of a Unique Marker to Identify Cells that can Control Transplant Rejection
Graft rejection results
from the immune system recognizing and damaging the transplanted organ, a
process that involves lymphocyte extravasation into
target organs. Because the inciting T cells recognize the transplant as
foreign, once at the site (e.g. kidney, pancreatic islets), they inflict damage
and release cytokines that recruit other leukocytes, ultimately resulting in
graft rejection. In contrast, regulatory T cells (Treg)
can prevent immune-mediated damage and thereby control chronic graft rejection.
Therefore, isolated Treg have great therapeutic
potential in prevention or reversal in a number of clinical situations,
including organ transplantation and autoimmune disease. Thus far, efforts to
use them have been hampered by small numbers, inability to select those most
relevant to an immunological process, such as transplant rejection, and only a
limited understanding of how they are distinct from effector
T cells. We have focused on the role of a form of the lymphocyte adhesion
receptor (CD44act) expressed on only a small fraction of activated T
cells and used to adhere to endothelial surfaces. We have shown that CD44act
is preferentially expressed on Treg and that Treg expressing CD44act are much more effective
in controlling damaging immune responses than Treg
not expressing it. Our data in mice indicate that CD44act identifies
T cells with a superior regulatory function that can prevent autoimmunity and allogeneic responses. We have also shown relevance of CD44act-bearing
T cells in human autoimmune disease, including Type 1 Diabetes. In renal
transplant patients, we will explore whether peripheral blood Treg express this marker post-transplantation and whether
it can be used to identify highly effective Treg
specifically protective for the transplanted organ. This may aid in therapies
that lead to augmentation of the preventative regulatory T cell response in a
variety of transplant situations.