Journal
BLOOD
Volume 115, Issue 13, Pages 2686-2694Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-07-229740
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Funding
- Swedish Foundation for Strategic Research
- Swedish Research Council
- Swedish Cancer Society
- Swedish Children's Cancer Foundation
- Cancer Society of Stockholm
- Royal Swedish Academy of Sciences
- Tobias Foundation
- Soderberg Foundation
- Belven Foundation
- Ake Wiberg Foundation
- Stockholm County Council
- Karolinska Institutet
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Natural killer (NK)-cell alloreactivity in recipients of hematopoietic stem cell grafts from HLA-identical siblings is intriguing and has suggested breaking of NK-cell tolerance during the posttransplantation period. To examine this possibility, we analyzed clinical outcomes in a cohort of 105 patients with myeloid malignancies who received T cell-replete grafts from HLA-matched sibling donors. Presence of inhibitory killer cell immunoglobulin-like receptors (KIRs) for nonself HLA class I ligands had no effect on disease-free survival, incidence of relapse, or graft-versus-host disease. A longitudinal analysis of the NK-cell repertoire and function revealed a global hyporesponsiveness of NK cells early after transplantation. Functional responses recovered at approximately 6 months after transplantation. Importantly, NKG2A(-) NK cells expressing KIRs for nonself HLA class I ligands remained tolerant at all time points. Furthermore, a direct comparison of NK-cell reconstitution in T cell-replete and T cell-depleted HLA-matched sibling stem cell transplantation (SCT) revealed that NKG2A(+) NK cells dominated the functional repertoire early after transplantation, with intact tolerance of NKG2A(-) NK cells expressing KIRs for nonself ligands in both settings. Our results provide evidence against the emergence of alloreactive NK cells in HLA-identical allogeneic SCT. (Blood. 2010;115(13):2686-2694)
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