NK cell effector functions in a Chédiak-Higashi patient undergoing cord blood transplantation: Effects of in vitro treatment with IL-2.
NK cell cytotoxicity in Chédiak-Higashi syndrome (CHS) is strongly impaired as lytic granules are not released upon NK-target cell contact, contributing to several defects typical of this severe immunodeficiency. Correction of NK cell defects in CHS should improve the outcome of hematopoietic stem-cell transplantation, proposed as therapy. We investigated NK cell functions in a CHS patient before and after cord-blood transplantation, and the ability of in vitro IL-2 treatment to restore them. Before the transplant, the strong defect in NK cell-mediated natural and antibody-dependent cytotoxicity, as well as in IFN-γ production, could be restored up to normal levels by in vitro IL-2 treatment. This cytokine also caused the appearance of smaller lysosomal granules and their orientation towards the NK-target cell contact area, thus suggesting that IL-2 had a more general capacity to restore NK cell effector functions. Moreover after the transplant, although the successful engraftment, NK cell cytotoxicity resulted still partially impaired at one year, almost normal at ten years and, anyhow, fully recovered by in vitro IL-2 treatment. Taken together, our results indicate that IL-2 had a wide capacity to restore NK cell effector functions, being able to reverse the altered cytotoxic activity, lytic granule pattern, and cytokine production observed in the CHS patient.
Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. Electronic address: loredana.cifaldi@opbg.net.
Loredana
L
Cifaldi
Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Rita Maria
RM
Pinto
Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Ippolita
I
Rana
Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Pediatric Oncohaematology Unit, Azienda Ospedaliera Universitaria Perugia, Italy.
Maurizio
M
Caniglia
Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Adriano
A
Angioni
Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Stefano
S
Petrocchi
University Department of Pediatrics, Bambino Gesù Children's Hospital and University of Tor Vergata, School of Medicine, Rome, Italy.
Caterina
C
Cancrini
Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Laura
L
Cursi
University Department of Pediatrics, Bambino Gesù Children's Hospital and University of Tor Vergata, School of Medicine, Rome, Italy.
Giuseppe
G
Palumbo
Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" University of Rome, Italy.
Alessandra
A
Zingoni
Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" University of Rome, Italy.
Angela
A
Gismondi
University Department of Pediatrics, Bambino Gesù Children's Hospital and University of Tor Vergata, School of Medicine, Rome, Italy.
Paolo
P
Rossi
Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" University of Rome, Italy.
Angela
A
Santoni
Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" University of Rome, Italy.
Cristina
C
Cerboni
D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D002460:Cell Line; D002609:Chediak-Higashi Syndrome / Q000188:drug therapy* / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male
D007376:Interleukin-2
Cellular immunology; Cord blood transplantation; Immunodeficiency; Interleukin 2; NK cells