Name of Student:
Alicia McMurchy
Research Supervisor: Dr. Megan Levings
Title of Presentation: Generation of human T regulatory cells with the capacity to suppress islet
allograft rejection in a humanized mouse model
Abstract
T regulatory cells (Tregs) have potential for use as a cellular therapy in organ transplantation,
but their application is hindered by difficulties in obtaining pure, sufficient numbers. We
previously developed a method to generate large, homogeneous populations of human Tregs
by transducing conventional T cells with lentivirus encoding the transcription factor FOXP3.
The purpose of the present study is to test the in vivo suppressive capacity of FOXP3transduced T cells in parallel to ex vivo expanded Tregs in a humanized mouse model of islet
allograft rejection. Human islets are transplanted into NODscid IL2rγnull (NSG) mice
previously treated with streptozotocin to induce diabetes. Once blood glucose levels have
normalized, indicating a functional graft, mice are injected with allogeneic human PBMCs to
initiate rejection, which is monitored on the basis of blood glucose. We were able to expand ex
vivo CD4+CD25hiCD45RA+ cells over 600-fold in two weeks by stimulating with artificial
antigen presenting cells in the presence of 100ng/mL rapamycin and 1000 U/mL IL-2 without
loss of FOXP3 expression. We have now established a robust model of islet allograft rejection
in NSG mice, and experiments are on-going to determine the in vivo suppressive capacities of
ex vivo expanded Tregs and FOXP3-transduced T cells. Evidence that human Tregs can
prevent rejection of human islets will provide a strong rationale for clinical translation of
cellular therapy to prevent allograft rejection.