title: Expansion of NKG2A-LIR1- natural killer cells in HLA-matched, killer cell immunoglobulin-like receptors/HLA-ligand mismatched patients following hematopoietic cell transplantation.
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.
authors.affiliation: Department of Hematology/Oncology, Freiburg University Hospital, Breisacher Strasse 115A, Freiburg, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rathmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Glatzel
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schönberg
authors.forename: Markus
authors.initials: M
authors.lastname: Uhrberg
authors.forename: Marie
authors.initials: M
authors.lastname: Follo
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz-Huotari
authors.forename: Markus
authors.initials: M
authors.lastname: Kaymer
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
authors.forename: Paul
authors.initials: P
authors.lastname: Fisch
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006680:HLA Antigens / Q000096:biosynthesis / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000276:immunology* / Q000628:therapy; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008223:Lymphoma / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000096:biosynthesis / Q000276:immunology*; D011379:Prognosis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D015703:Antigens, CD; D006680:HLA Antigens; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic