16 research outputs found
NK cell alloreactivity is an important mediator of costimulation-blockade-resistant rejection during allogeneic transplantation
Dissecting the Mechanisms of GvHD Control: Using the Primate GvHD Model to Determine the Role That Sirolimus Plays in GvHD Prevention
Magnetotransport and electrical properties of colossal magnetoresistive La0.8Sr0.2Mn03 at different sintering temperature.
Structural, electrical and magnetoresistance of La 0.7Ca0.28 Sr0.02Mn03 at different sintering temperatures.
Rhesus Macaque Natural CD4 Regulatory T Cells Exhibit Decreased Proliferation But Enhanced Suppression After Pulsing with Sirolimus
NK cells mediate costimulation blockade-resistant rejection of allogeneic stem cells during nonmyeloablative transplantation
Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism to promote immune tolerance during murine allotransplantation, it has not yet been successfully translated to clinical transplantation. We determined the impact of natural killer (NK) cells on costimulation blockade-resistant rejection of donor bone marrow. We found that NK cells represent a potent barrier to engraftment: host NK depletion led to increased donor stem cell survival, increased mixed hematopoietic chimerism and to engraftment of low doses of donor marrow (1 × 108/kg) that were otherwise rejected. To understand the mechanisms of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We found that an increased proportion of target cells were killed between days 2 and 8 after cell transfer, and that NK killing of parental targets was inducible: NK cells preprimed with allotargets were more efficient at their elimination upon reexposure. Finally, both transplant and in vivo NK-killing models were used to determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led to decreased NK-mediated killing, and increased alloengraftment. These results identify NK alloreactivity as an integral component to costimulation blockade-resistant rejection, and suggest that its inhibition may represent an important target in the clinical translation of tolerance-induction transplantation