Expansion of NKG2A-LIR1- natural killer cells in HLA-matched, killer cell immunoglobulin-like receptors/HLA-ligand mismatched patients following hematopoietic cell transplantation

Biol Blood Marrow Transplant. 2010 Apr;16(4):469-81. doi: 10.1016/j.bbmt.2009.12.008. Epub 2010 Jan 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology*
  • Female
  • Flow Cytometry / methods
  • HLA Antigens / biosynthesis
  • HLA Antigens / immunology*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Killer Cells, Natural / immunology*
  • Leukemia / immunology*
  • Leukemia / therapy
  • Leukocyte Immunoglobulin-like Receptor B1
  • Lymphoma / immunology*
  • Lymphoma / therapy
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily C / biosynthesis
  • NK Cell Lectin-Like Receptor Subfamily C / immunology*
  • Prognosis
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / immunology*
  • T-Lymphocyte Subsets / immunology


  • Antigens, CD
  • HLA Antigens
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Immunologic