Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation

Interactions between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands influence development of natural killer (NK) bell repertoire and response to infection, cancer, and allogeneic tissue. As KIRs and HLA class I molecules are highly polymorphic, clinical allogeneic hematopoietic cell transplantation is predicted to frequently involve KIR mismatch, and thus to provide a unique system for study of human NK cell receptor repertoire development. Eighteen leukemia patients undergoing HLA-matched transplantation and their donors were analyzed for KIR genotype. Ten of 13 HLA-identical donor-patient pales were KIR mismatched and 3 were matched; all HLA-matched unrelated pales were KIR mismatched. Reconstitution of recipient NK cell repertoire following transplantation was examined using flow cytometry and monoclonal antibodies specific for KIR and CD94: NKG2A. These data form 3 groups. Six to 9 months after transplantation, 8 patients (group 1) reconstituted an NK cell repertoire resembling that of their donor, and for KIR-mismatched transplants,. distinct from the recipient before transplantation. In the first year after transplantation, 5 patients (group 2) exhibited a generally depressed frequency of KIR-expressing NK cells and concomitant high frequency of CD94:NKG2A expression. By 3 years after transplantation, the frequency of KIR-expressing NK cells had. increased to donor values, in the 3 patients from group 2 analyzed for this period. The remaining 5 patients experienced severe, clinical complications following transplantation and displayed unique features in their NK dell receptor reconstitution. These results demonstrate that a majority of HLA-matched hematopoietic bell transplantations involve KIR mismatch and reveal differences in NK cell repertoire having potential impact, for immune responsiveness and transplantation outcome. (C) 2003 by The American Society of Hematology.