Evaluation of the tolerogenic effects of donor bone marrow cells using a severe combined immunodeficient mouse-human islet transplant model

It was observed that the most cellularly economical dose was 3000 islets per animal and that injection into the portal vein was better than implantation under the kidney capsule. Even though maximal lymphoid reconstitution was observed with 40-million fresh and anti-CD3 activated recipient PBL (conventional method), the mice developed severe graft GvHD. However, with the new method of reconstitution where animals were injected with 20-million anti-CD3-activated plus 40-million anti-donor-activated recipient PBL, no discernible GvHD was observed. More importantly, this latter method was associated with islet transplant rejection, which in turn could be abrogated by co-injection of the animals with DBMC. These in vivo results confirmed our previous in vitro observations that human DBMC have regulatory activity.