title: Visualization of the human CD4⁺ T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/γc(null) (NOG) mice by retrogenic expression of the human TCR gene.
abstract: The development of severe immunodeficient mouse strains containing various human genes, including cytokines or HLA, has enabled the reconstitution of functional human immune systems after transplantation of human hematopoietic stem cells (HSC). Accumulating evidence has suggested that HLA-restricted antigen-specific human T-cell responses can be generated in these humanized mice. To directly monitor immune responses of human CD4(+) T cells, we introduced β-lactoglobulin (BLG)-specific T cell receptor (TCR) genes derived from CD4(+) T-cell clones of cow-milk allergy patients into HSCs, and subsequently transplanted them into NOG-HLA-DR4 transgenic/I-Aβ deficient mice (NOG-DR4/I-A(o)). In the thymus, thymocytes with BLG-specific TCR preferentially differentiated into CD4(+)CD8(-) single-positive cells. Adoptive transfer of mature CD4(+) T cells expressing the TCR into recipient NOG-DR4/I-A(o) mice demonstrated that human CD4(+) T cells proliferated in response to antigenic stimulation and produced IFN-γ in vivo, suggesting that functional T-cell reactions (especially Th1-skewed responses) were induced in humanized mice.
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan. Electronic address: takeshi-takahashi@ciea.or.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Katano
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ito
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D049109:Cell Proliferation; D017690:Cell Transplantation; D058501:Enzyme-Linked Immunospot Assay; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007782:Lactoglobulins / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D060168:Thymocytes / Q000166:cytology
chemical_list: D018952:Antigens, CD34; D015804:HLA-DR4 Antigen; D007782:Lactoglobulins; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma
keywords: HLA-DR4; Humanized mice; NOG mice; TCR; Th1