NK cell killer immunoglobulin receptor (KIR) reconstitution and interferon production after unrelated donor (URD) transplantation is altered by the T-cell content of the graft and correlates with acute GVHD

Abstract

KIR ligand mismatched haploidentical T-cell depleted (TCD) transplants prevent AML relapse, GVHD, and graft failure, but similar outcomes are not achieved with the same strategy when T-cell- replete (non-TCD) grafts are used. We hypothesized that the variable clinical benefit is due to differences in KIR reconstitution and NK cell function affected by competing donor T cells, which may dilute the benefit of NK-cell alloreactivity. We studied cryopreserved PBLs collected by the National Marrow Donor Program Research Sample Repository from 93 URD transplant recipients (48 TCD, 45 non-TCD) and their donors, who provide perfect controls for the genetic determinants of the KIR repertoire.