title: Development of a human adaptive immune system in cord blood cell-transplanted mice.
abstract: Because ethical restrictions limit in vivo studies of the human hemato-lymphoid system, substitute human to small animal xenotransplantation models have been employed. Existing models, however, sustain only limited development and maintenance of human lymphoid cells and rarely produce immune responses. Here we show that intrahepatic injection of CD34+ human cord blood cells into conditioned newborn Rag2-/-gammac-/- mice leads to de novo development of B, T, and dendritic cells; formation of structured primary and secondary lymphoid organs; and production of functional immune responses. This provides a valuable model to study development and function of the human adaptive immune system in vivo.
authors.affiliation: Institute for Research in Biomedicine (IRB), Via Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Traggiai
authors.forename: Laurie
authors.initials: L
authors.lastname: Chicha
authors.forename: Luca
authors.initials: L
authors.lastname: Mazzucchelli
authors.forename: Lucio
authors.initials: L
authors.lastname: Bronz
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Piffaretti
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology*; D015329:Gene Rearrangement, T-Lymphocyte; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007136:Immunoglobulins / Q000032:analysis; D007231:Infant, Newborn; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D007136:Immunoglobulins; D013745:Tetanus Toxoid