Research Group

  • Dr Donna L. Farber, Principal Investigator
  • Dr Anita Tang, Research Associate
  • Dr Richard N. Pierson III, Collaborator

Location

  • University of Maryland School of Medicine, Baltimore, USA

Title

  • The Role of Memory T Cells in Transplant Rejection

Transplantation of kidneys, liver, pancreas, heart and lungs is highly effective in treating individuals with irreversible organ damage; however, survival of organ transplants beyond five years remains low (50-70%). The major barrier to long-term organ survival in transplantation is the individual’s own immune system, specifically T cells, which mount rigorous immune responses to non-self tissue, or alloantigens. Currently, transplant recipients must be maintained on potent drugs to suppress T cells; however, grafts are often eventually rejected, and this rejection occurs more readily in individuals that have been previously exposed to alloantigens by a prior transplant, pregnancy, blood transfusion, or infection, and therefore contain primed cells called “memory T cells”. Memory T cells persist over the lifetime of an individual, exhibit robust responses to recall antigens and mediate accelerated graft rejection compared to naive T cells that have not previously been activated. Importantly, in adult transplant patients, the majority of circulating T cells are memory T cells. Currently, the role of memory T cells in transplant rejection remains undefined, and the effect of immunosuppressive therapies on memory T cells is not known, as they are targeted to inhibit activation of naive T cells. In the proposed research, we will use our novel mouse model, called the “Mosaic-memory mouse” containing a marked population of alloreactive memory T cells to investigate how rejection of heart and skin allografts may be altered when graft-specific memory T cells are present, and whether memory T cells are susceptible to current immunosuppressive and T cell-depletion therapies. Results from the proposed studies will provide crucial insight into the role of the important and prevalent memory T cell subset in transplant recipients and will lead to improved and more targeted strategies for promoting long-term survival of transplanted organs.

Final Report