PMID- 12511415 OWN - NLM STAT- MEDLINE DCOM- 20030620 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 101 IP - 9 DP - 2003 May 1 TI - Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation. PG - 3730-40 AB - 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. FAU - Shilling, Heather G AU - Shilling HG AD - Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. FAU - McQueen, Karina L AU - McQueen KL FAU - Cheng, Nathalie W AU - Cheng NW FAU - Shizuru, Judith A AU - Shizuru JA FAU - Negrin, Robert S AU - Negrin RS FAU - Parham, Peter AU - Parham P LA - eng GR - AI07290/AI/NIAID NIH HHS/United States GR - CA49605/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030102 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (HLA Antigens) RN - 0 (KLRC1 protein, human) RN - 0 (KLRD1 protein, human) RN - 0 (Lectins, C-Type) RN - 0 (NK Cell Lectin-Like Receptor Subfamily C) RN - 0 (NK Cell Lectin-Like Receptor Subfamily D) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, KIR) RN - 0 (Receptors, Natural Killer Cell) SB - IM MH - Acute Disease MH - Adult MH - Antigens, CD/*genetics/immunology MH - Cell Lineage MH - Cytotoxicity, Immunologic MH - Female MH - Follow-Up Studies MH - Genotype MH - Graft Survival MH - Graft vs Host Disease/etiology/immunology MH - HLA Antigens/genetics MH - Histocompatibility MH - Humans MH - Killer Cells, Natural/*cytology/immunology MH - Lectins, C-Type/*genetics/immunology MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy MH - Leukemia, Myeloid/therapy MH - Male MH - Middle Aged MH - NK Cell Lectin-Like Receptor Subfamily C MH - NK Cell Lectin-Like Receptor Subfamily D MH - *Peripheral Blood Stem Cell Transplantation/adverse effects MH - Receptors, Immunologic/*genetics/immunology MH - Receptors, KIR MH - Receptors, Natural Killer Cell MH - Remission Induction MH - Transplantation Chimera MH - Transplantation, Homologous/adverse effects/immunology MH - Treatment Outcome EDAT- 2003/01/04 04:00 MHDA- 2003/06/21 05:00 CRDT- 2003/01/04 04:00 PHST- 2003/01/04 04:00 [pubmed] PHST- 2003/06/21 05:00 [medline] PHST- 2003/01/04 04:00 [entrez] AID - S0006-4971(20)50762-3 [pii] AID - 10.1182/blood-2002-08-2568 [doi] PST - ppublish SO - Blood. 2003 May 1;101(9):3730-40. doi: 10.1182/blood-2002-08-2568. Epub 2003 Jan 2.