NK cells expressing inhibitory KIR for non–self-ligands remain tolerant in HLA-matched sibling stem cell transplantation

AT Björklund, M Schaffer, C Fauriat… - Blood, The Journal …, 2010 - ashpublications.org
AT Björklund, M Schaffer, C Fauriat, O Ringdén, M Remberger, C Hammarstedt, AJ Barrett
Blood, The Journal of the American Society of Hematology, 2010ashpublications.org
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 …
Abstract
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.
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