title: Intra-thymic/splenic engraftment of human T cells in HLA-DR1 transgenic NOD/scid mice.
abstract: A HLA-DR1 transgenic mouse (NOD/scid-DR1) was derived by breeding the existing B10.M/J-[Tg]DR1 mouse with the NOD/scid mouse. The intention was to enhance engraftment of human T cells by providing human class II elements in the tissues. Thymus and spleen fragments from adult NOD/scid-DR1 mice were transplanted under the syngeneic kidney capsules, followed by injection of human cord blood mononuclear cells (CBMNC) into transplanted tissues. FACS analyses showed that human T and B cells were consistently detected in the peripheral blood and spleen, of the chimeric mice. An average of 20% of human cells was found in the spleen and the engrafted thymus/spleen tissues. Furthermore, human cells from these tissues could proliferate with anti-human CD3 antibody and these mice could generate humoral and cellular responses to allogeneic human cells. Cytokines, such as IL-10, GMCSF, IFN-gamma, and TNF-alpha were also detected in the supernatants of the cultured human cells from the chimeric mice, when they were stimulated with allogeneic cells. Therefore, a novel mouse model with functional circulating human T and B cells was established that would facilitate the exploration of vaccine, the disease processes of autoimmunity, HIV infection, and human cancer.
authors.affiliation: Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: Ramon E
authors.initials: RE
authors.lastname: Camacho
authors.forename: Richard
authors.initials: R
authors.lastname: Wnek
authors.forename: Kashmira
authors.initials: K
authors.lastname: Shah
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Zaller
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: Nancy
authors.initials: N
authors.lastname: Collins
authors.forename: Patricia
authors.initials: P
authors.lastname: Fitzgerald-Bocarsly
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Koo
mesh_terms: D000818:Animals; D006085:Graft Survival / Q000276:immunology; D015798:HLA-DR1 Antigen / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D015798:HLA-DR1 Antigen