title: Effects of human interleukin-18 and interleukin-12 treatment on human lymphocyte engraftment in NOD-scid mouse.
abstract: NOD/LtSz-prkdc(scid)/prkdc(scid) (non-obese diabetic-severe combine immunodeficiency; NOD-scid) mice grafted with human peripheral blood lymphoid cells have been used as an in vivo humanized mouse model in various studies. However, cytotoxic human T cells are induced in this model during immune responses, which gives misleading results. To assist in grafting of human lymphocytes without the induction of cytotoxic human T cells, we investigated the effects of T helper type 1 (Th1) and Th2 cytokines on human lymphocyte grafting and migration, as well as the production of immunoglobulin deposited in glomeruli and human immunodeficiency virus-1 (HIV-1) infection using NOD-scid mice. Administration of interleukin-18 (IL-18) and IL-12 enhanced the grafting of human CD4+ and CD8+ T cells in the mice, whereas co-administration prevented grafting due to interferon-gamma-dependent apoptosis. Immunoglobulin A (IgA) deposits were observed in mice treated with IL-18 alone, but not in those given phosphate-buffered saline, IL-12 alone, or IL-18 + IL-12. A high rate of HIV infection was also observed in the IL-18-treated group. Together, these results indicate that IL-18 may be effective for the grafting and migration of CD4+ and CD8+ T cells, except for the induction of apoptosis and regulation of class-switching IgA. IL-18-administered NOD-scid mice provide a useful small humanized model for the study of HIV infection and IgA nephropathy.
authors.affiliation: Department of Oral Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8650, Japan. hsenpuku@noh.go.jp
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Senpuku
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Asano
authors.forename: Khairul
authors.initials: K
authors.lastname: Matin
authors.forename: M Abdus
authors.initials: MA
authors.lastname: Salam
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Tsuha
authors.forename: Shigeo
authors.initials: S
authors.lastname: Horibata
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Shimazu
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Soeno
authors.forename: Takaaki
authors.initials: T
authors.lastname: Aoba
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Hanada
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Honda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D017710:Lymphocyte Transfusion; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012367:RNA, Viral / Q000032:analysis; D014183:Transplantation, Heterologous
chemical_list: D020382:Interleukin-18; D007378:Interleukins; D012367:RNA, Viral; D018664:Interleukin-12; D007371:Interferon-gamma