In murine studies effective prevention of GvHD without abrogating GvT is possible by co-administration of Foxp3+ regulatory T cells (Tregs) with the transplants. Consistent with this work, we have recently shown that human Tregs can downregulate GvHD in a xenogeneic model in the RAG2-/-γc-/- mice. Towards clinical application of Tregs for GvHD prevention, we are exploring whether Treg-administration influences the GvT effect. To this end, we use two complementary approaches:
a) in vitro studies. Here we analyse the numbers/activities of Tregs in PBMC and biopsy samples from a large panel of leukemia and myeloma patients and correlate these data with the clinical outcome.
b) In vivo studies: Here the effect of Treg-administration on GvT is tested using bioluminescence imaging (BLI)-based GvT models in the RAG2-/-γc-
/- mice. The GvT models. We recently demonstrated that co-administration of Tegs with effector T cells do not downregulate GvT while significantly inhibiting GvHD ( manuscript in preparation). Current efforts are focusing on delineating the mechanisms of the GvT/GvHD separation by Tregs.