Defining the optimal plasmacytoid dendritic cell graft source for hematopoietic stem cell transplantation

Abstract

Abstract Purpose Allogeneic hematopoietic stem cell transplantation (HSCT) can cure patients with blood disorders and malignancies. Stem cell source can be bone marrow (BM) or peripheral blood mobilized by granulocyte-colony stimulating factor (G-CSF). Plasmacytoid dendritic cells (pDC) reduce the incidence and severity of GvHD. The BMT CTN 0201 study indicates overall survival, relapse, and the incidence of acute GvHD are similar in patients that receive BM versus G-CSF mobilized peripheral blood (G-PB) grafts, but increased incidence of chronic GvHD in patients who receive G-PB grafts. To explore the effect of graft source on the functional properties of pDC, we compared the effect of G-CSF mobilized pDC to BM pDC in the regulation of GvHD in a murine allogeneic HSCT model. Methods 1) Expression of surface markers on BM and G-CSF treated pDC were assessed by flow cytometry. 2) We performed an HSCT from C57BL/6 mice into B10.BR recipients. Groups include HSC only, HSC + T cells, and HSC + T cells + BM pDC or G-CSF mobilized pDC. Hematopoietic chimerism, GvHD, and overall survival were assessed. Results 1) BM pDC express CCR9 (marker for tolerogenic pDC) and CD62L at a higher frequency, suggesting enhanced homing to the gut, thymus, and lymph nodes. G-CSF mobilized pDC express maturational markers MHC II and CD86 at a higher frequency, suggesting effectiveness in activating T cells. 2) Mice that received transplants consisting of only HSC rejected the transplant. Mice that received transplants with T cells had greater than 90% donor hematopoietic cells. GvHD more than 40 days post transplant was highest in mice that received G-CSF mobilized pDC. Survival without pDC was under 60%. Groups that received pDC had an overall survival of greater than 80%.