title: Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent.
abstract: SCID-hu mice are heterochimeric animals that are constructed by transplanting human fetal thymus (Thy), liver (Liv), and/or lymph nodes into congenitally immunodeficient C.B-17 scid/scid (SCID) mice. Sensitive and specific two-color flow cytometric assays were used to evaluate human lymphocytes from peripheral blood of SCID-hu mice. Kinetic studies presented in this report show long term T lymphopoiesis in SCID-hu mice. Approximately one-half of SCID-hu mice constructed with Thy and Liv tissue develop detectable levels of circulating human T cells by 4 mo after transplantation. The average level of circulating human cells in SCID-hu mice is generally less than 2% of the total lymphoid cells in the peripheral blood of these mice. Some SCID-hu mice with as high as 13% human lymphocytes, however, have been detected. Nearly all human cells in the peripheral blood of SCID-hu mice are CD3+ cells that express TCR-alpha beta. The percentages of gamma delta+, CD4+, CD8+, CD25+, CD69+, and Leu-8+ cells among CD45+ cells in SCID-hu blood are similar to the levels found in adult peripheral blood. On average, 74% of SCID-hu T cells express CD45RA and 18% express CD29. Functional studies demonstrate that cells from SCID-hu Thy/Liv grafts or human T cells from SCID-hu peripheral blood are functionally competent to respond to mitogens or allogeneic human cells in vitro. They are similar to fetal thymocytes or adult T cells, respectively, in these responses. These studies demonstrate that the SCID-hu mouse is a useful model for the analysis of human immune differentiation and function in vivo.
authors.affiliation: SyStemix, Inc., Palo, Alto, CA 94303.
authors.forename: J F
authors.initials: JF
authors.lastname: Krowka
authors.forename: S
authors.initials: S
authors.lastname: Sarin
authors.forename: R
authors.initials: R
authors.lastname: Namikawa
authors.forename: J M
authors.initials: JM
authors.lastname: McCune
authors.forename: H
authors.initials: H
authors.lastname: Kaneshima
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D005333:Fetus; D006649:Histocompatibility Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000637:transplantation; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens