title: Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice.
abstract: The scid mutation was backcrossed on to the NOD/Shi mouse background, resulting in the development of NOD/Shi-scid mice, which showed lack of mature lymphocytes, macrophage dysfunction and absence of circulating complement, but were not as impaired in natural killer (NK) cell activity as NOD/LtSz-scid mice. We then examined the effect of recipient NK cell depletion by anti-asialo GM1 antiserum on the repopulation of human cord blood (CB) hematopoietic stem cells (HSC) in NOD/Shi-scid mice to clarify the role of recipient NK cells in human HSC engraftment. The anti-asialo GM1 antiserum treatment significantly enhanced the engraftment of CB CD34+ cells, but did not affect the differentiation of the engrafted HSC into each hematopoietic lineage. The NK cell depletion was effective at early stages of the engraftment, but not 3 weeks after the transplantation. The anti-asialo GM1 antiserum treatment did not improve the engraftment by human HSC in scid mice which lack mature lymphocytes, but show neither macrophage dysfunction nor a reduction in circulating complement, indicating that macrophages and/or complement also have roles in HSC graft rejection. The present study indicates that the preconditioning targeting of recipient NK cells in addition to T cell suppression and myeloablation might prevent HSC graft failure, and that NOD/Shi-scid mice treated with anti-asialo GM1 antiserum could provide a useful tool for evaluating the repopulating ability of transplantable human HSC.
authors.affiliation: Department of Clinical Oncology, The Institute of Medical Science, The University of Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshino
authors.forename: T
authors.initials: T
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Kawahata
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ebihara
authors.forename: A
authors.initials: A
authors.lastname: Manabe
authors.forename: R
authors.initials: R
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Asano
authors.forename: T
authors.initials: T
authors.lastname: Nakahata
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism; D005312:Fetal Blood / Q000276:immunology; D005677:G(M1) Ganglioside / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007178:Inbreeding; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D019172:Transplantation Conditioning / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D007106:Immune Sera; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D003165:Complement System Proteins