Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity
| Autor: | Céline Cognet, Rita Maccario, Maria Ester Bernardo, Daniela Pende, Michela Falco, Maria Cristina Mingari, Franco Locatelli, Miryam Martinetti, Elisa Romeo, Stefania Martini, Lorenzo Moretta, Stefania Marcenaro, Daniela Montagna, Eric Vivier, Alessandro Moretta |
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| Přispěvatelé: | Istituto Nazionale per la Ricerca sul Cancro, Genova, Immunologia, Università di Genova, Dipartimento di Medicina Sperimentale, Istituto Giannina Gaslini, Genova, Immunologia Clinica e Sperimentale, Università degli Studi di Pavia, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Pavia = University of Pavia (UNIPV), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pende, D, Marcenaro, S, Falco, M, Martini, S, Bernardo, M, Montagna, D, Romeo, E, Cognet, C, Martinetti, M, Maccario, R, Mingari, Mc, Vivier, E, Moretta, L, Locatelli, F, Moretta, A |
| Rok vydání: | 2008 |
| Předmět: |
Male
MESH: Tissue Donors medicine.medical_treatment KIR Ligand Hematopoietic stem cell transplantation Biochemistry Substrate Specificity Interleukin 21 0302 clinical medicine Receptors KIR hemic and lymphatic diseases MESH: Child Child Cells Cultured 0303 health sciences Leukemia biology Histocompatibility Testing Hematopoietic Stem Cell Transplantation Hematology MESH: Transplantation Tissue Donors 3. Good health Killer Cells Natural MESH: Young Adult Child Preschool [SDV.IMM]Life Sciences [q-bio]/Immunology Female Antibody MESH: Cells Cultured MESH: Killer Cells Natural Adolescent Immunology Graft vs Leukemia Effect Human leukocyte antigen MESH: Histocompatibility Testing 03 medical and health sciences Young Adult KIR2DL1 MESH: Receptors KIR MESH: Leukemia medicine MESH: Transplantation Homologous Humans Transplantation Homologous MESH: Patient Selection MESH: Hematopoietic Stem Cell Transplantation 030304 developmental biology MESH: Adolescent Transplantation MESH: Humans Patient Selection MESH: Child Preschool Cell Biology MESH: Graft vs Leukemia Effect medicine.disease MESH: Male biology.protein MESH: Substrate Specificity MESH: Female 030215 immunology |
| Zdroj: | Blood Blood, American Society of Hematology, 2009, 113 (13), pp.3119-29. ⟨10.1182/blood-2008-06-164103⟩ Blood, 2009, 113 (13), pp.3119-29. ⟨10.1182/blood-2008-06-164103⟩ |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2008-06-164103⟩ |
| Popis: | We analyzed 21 children with leukemia receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) from killer immunoglobulin (Ig)–like receptors (KIR) ligand-mismatched donors. We showed that, in most transplantation patients, variable proportions of donor-derived alloreactive natural killer (NK) cells displaying anti-leukemia activity were generated and maintained even late after transplantation. This was assessed through analysis of donor KIR genotype, as well as through phenotypic and functional analyses of NK cells, both at the polyclonal and clonal level. Donor-derived KIR2DL1+ NK cells isolated from the recipient displayed the expected capability of selectively killing C1/C1 target cells, including patient leukemia blasts. Differently, KIR2DL2/3+ NK cells displayed poor alloreactivity against leukemia cells carrying human leukocyte antigen (HLA) alleles belonging to C2 group. Unexpectedly, this was due to recognition of C2 by KIR2DL2/3, as revealed by receptor blocking experiments and by binding assays of soluble KIR to HLA-C transfectants. Remarkably, however, C2/C2 leukemia blasts were killed by KIR2DL2/3+ (or by NKG2A+) NK cells that coexpressed KIR2DS1. This could be explained by the ability of KIR2DS1 to directly recognize C2 on leukemia cells. A role of the KIR2DS2 activating receptor in leukemia cell lysis could not be demonstrated. Altogether, these results may have important clinical implications for the selection of optimal donors for haplo-HSCT. |
| Databáze: | OpenAIRE |
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