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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-08-2568.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3730-3740
TRANSPLANTATION
Reconstitution of NK cell receptor repertoire following
HLA-matched hematopoietic cell transplantation
Heather G. Shilling,
Karina
L. McQueen,
Nathalie W. Cheng,
Judith A. Shizuru,
Robert S. Negrin, and
Peter Parham
From the Departments of Structural Biology, and
Microbiology and Immunology, Stanford University School of Medicine,
Stanford, CA; and the Department of Medicine, Stanford University
School of Medicine, Stanford, CA.
Interactions between killer immunoglobulin-like receptors (KIRs)
and human leukocyte antigen (HLA) class I ligands influence development
of natural killer (NK) cell 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 pairs were KIR
mismatched and 3 were matched; all HLA-matched
unrelated pairs 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 cell receptor
reconstitution. These results demonstrate that a majority of
HLA-matched hematopoietic cell transplantations involve
KIR mismatch and reveal differences in NK cell repertoire
having potential impact for immune responsiveness and
transplantation outcome.

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