Effects of human interleukin-18 and interleukin-12 treatment on human lymphocyte engraftment in NOD-scid mouse.
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.
Senpuku
Hidenobu
H
Department of Oral Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8650, Japan. hsenpuku@noh.go.jp
Asano
Toshihiko
T
Matin
Khairul
K
Salam
M Abdus
MA
Tsuha
Yuzo
Y
Horibata
Shigeo
S
Shimazu
Yoshihito
Y
Soeno
Yuichi
Y
Aoba
Takaaki
T
Sata
Tetsutaro
T
Hanada
Nobuhiro
N
Honda
Mitsuo
M
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
D020382:Interleukin-18; D007378:Interleukins; D012367:RNA, Viral; D018664:Interleukin-12; D007371:Interferon-gamma