Development of a human adaptive immune system in cord blood cell-transplanted mice.
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.
Traggiai
Elisabetta
E
Institute for Research in Biomedicine (IRB), Via Vela 6, 6500 Bellinzona, Switzerland.
Chicha
Laurie
L
Mazzucchelli
Luca
L
Bronz
Lucio
L
Piffaretti
Jean-Claude
JC
Lanzavecchia
Antonio
A
Manz
Markus G
MG
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
D018952:Antigens, CD34; D007136:Immunoglobulins; D013745:Tetanus Toxoid