Article ID Journal Published Year Pages File Type
2104323 Biology of Blood and Marrow Transplantation 2010 13 Pages PDF
Abstract

The prognosis after hematopoietic cell transplantation (HCT) for the treatment of leukemia or lymphoma in humans is influenced by donor-derived natural killer (NK) cells, which enhance the graft-versus-leukemia (GVL) effect. Such alloreactive killer cells can be generated in vivo after HCT if the donor expresses killer cell immunoglobulin-like receptors (KIRs), such as KIR2DL1, KIR2DL2/3, or KIR3DL1, for which the recipient lacks HLA class I ligands. We studied effector cells from 22 KIR/HLA-ligand mismatched and 14 KIR/HLA-ligand matched, primarily HLA-matched patient-donor pairs after allogeneic HCT. A novel 8-color flow cytometry panel allowed us to characterize effector-cell populations without “broadly reactive” inhibitory receptors such as CD94/NKG2A or LIR1. The numbers of such NKG2A– LIR1– NK cells increased following HCT in patients transplanted by KIR/HLA-ligand mismatched grafts, compared to KIR/HLA-ligand matched grafts, and in patients transplanted from donors of the A/B, compared to A/A, KIR haplotypes. NKG2A–LIR1– NK cells expressing only those inhibitory KIRs for which the patient had no HLA class I ligands could be stimulated by HLA class I-deficient cells to express CD107a. Thus, NKG2A–LIR1– NK cells may be important GVL effector cells following HCT, even in patients transplanted from HLA-matched donors.

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