title: Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34(+) cells.
abstract: The NOD-LtSZ scid/scid (NOD/SCID) repopulation assay is the criterion for the study of self-renewal and multilineage differentiation of human hematopoietic stem cells. An important shortcoming of this model is the reported absence of T-cell development. We studied this aspect of the model and investigated how it could be optimized to support T-cell development. Occasionally, low-grade thymic engraftment was observed in NOD/SCID mice or Rag2(-/-)gamma(c)(-/-) mice. In contrast, the treatment of NOD/SCID mice with a monoclonal antibody against the murine interleukin-2R beta, (IL-2R beta) known to decrease natural killer cell activity, resulted in human thymopoiesis in up to 60% of the mice. T-cell development was phenotypically normal and resulted in polyclonal, mature, and functional CD1(-) TCR alpha beta (+) CD4(+) or CD8(+) single-positive T cells. In mice with ongoing thymopoiesis, peripheral T cells were observed. TREC analysis showed that T cells with a naive phenotype (CD45RA(+)) emerged from the thymus. In approximately half of these mice, the peripheral T cells included a pauciclonal outgrowth of CD45RO(+) cells. These data suggest that all elements of a functional immune system were present in these animals.
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University Hospital, Belgium. tessa.kerre@rug.ac.be
authors.forename: Tessa C C
authors.initials: TC
authors.lastname: Kerre
authors.forename: Greet
authors.initials: G
authors.lastname: De Smet
authors.forename: Magda
authors.initials: M
authors.lastname: De Smedt
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
authors.forename: Mikaël J
authors.initials: MJ
authors.lastname: Pittet
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: José
authors.initials: J
authors.lastname: De Bosscher
authors.forename: Fritz
authors.initials: F
authors.lastname: Offner
authors.forename: Bart
authors.initials: B
authors.lastname: Vandekerckhove
authors.forename: Jean
authors.initials: J
authors.lastname: Plum
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D018952:Antigens, CD34; D002454:Cell Differentiation; D005312:Fetal Blood / Q000166:cytology; D006085:Graft Survival / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D019891:Leukopoiesis / Q000187:drug effects*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
chemical_list: D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D015375:Receptors, Interleukin-2