作者: Sandeep Chunduri , Dolores Mahmud , Javaneh Abbasian , Damiano Rondelli
DOI: 10.1182/BLOOD.V106.11.2203.2203
关键词:
摘要: Transplantation of HLA-mismatched cord blood (CB) nucleated cells has limited risk severe acute graft-versus-host disease and graft rejection. This may depend on naive T not yet exposed to many antigens immature antigen-presenting (APC) delivering appropriate signals allogeneic cells. In order test the APC activity human circulating CB in-vitro, we initially used irradiated mononuclear (MNC) or immunomagnetically selected CD34+ cells, CD133+ CD14+ monocytes stimulate proliferative response incompatible in mixed leukocyte culture (MLC). MNC failed induce cell proliferation, while progenitors induced potent alloresponses. Nevertheless, since was restored after depletion CD3+ CB, nor add-back stimulators inhibited allo-T a direct suppressive effect excluded. Allogeneic peripheral cytotoxic T-lymphocyte (CTL) responses were 7 days stimulation with MNC, although 4 weekly rechallenges average 23% lysis antigen-specific PHA-blasts observed at highest effector:target ratio (50:1). To tolerogenic potential rechallenged secondary MLC monocyte-derived dendritic (Mo-DC) generated liquid GM-CSF IL-4. still unresponsive upon rechallenge but proliferated 3 restimulation Mo-DC from same CB. Surprisingly, supernatant these latter MLCs did inhibit completely 3rd party MLC. Instead, that had been activated by both primary not. These results show an impaired allo-APC suggest releasing immunosuppressive cytokines be then expanded second more professional APC. hypothesis could explain sustained engraftment stem transplants humans. Based results, in-vivo ex-vivo downregulation alloreactivity will tested experimental models cell, as well solid organ transplantation.