title: Roles of NKT cells in resistance against infection with Toxoplasma gondii and in expression of heat shock protein 65 in the host macrophages.
abstract: We investigated the roles of gamma delta T, NK, and NK1.1(+) T-like (NKT) cells in protective immunity against infection with Toxoplasma gondii. gamma delta T cells, NKT and NK cells, and NK cells in BALB/c mice were depleted by treatment with anti-TCR-gamma delta monoclonal antibody (mAb), anti-interleukin-2 receptor beta chain (IL-2R beta) mAb, and anti-asialoGM1 Ab, respectively, and these mice were infected with T. gondii. Treatment of mice with anti-TCR-gamma delta mAb aggravated toxoplasmosis, while treatment with anti-asialoGM1 Ab had no effects. Treatment with anti-IL-2R beta mAb enhanced the expression of heat shock protein 65 (HSP65) and gamma interferon (IFN-gamma) mRNA, while it inhibited interleukin-4 (IL-4) mRNA expression, ameliorating toxoplasmosis. In addition to NK cells, anti-IL-2R beta mAb eliminated cells expressing IL-2R beta and intermediate levels of CD3 (IL-2R beta(+) CD3(int)). Mice treated with anti-IL-2R beta mAb decreased the number of DX5(+) CD3(int) cells, which are considered to be equivalent to NK1.1(+)T cells in NK1.1 allele-negative strains. IL-2R beta(+) CD3(int) cells isolated from splenic and hepatic lymphoid cells were confirmed to express the TCR-V alpha 14 transcript. The magnitude of HSP65 induction in macrophages correlated with the protective potential against T. gondii infection after treatment with the antibodies, supporting our previous finding that gamma delta T cells play an essential role in the induction of HSP65 in host macrophages. Interestingly, NKT cells suppressed the expression of gamma delta T cell-induced HSP65 and IFN-gamma. Furthermore, depletion of IL-2R beta(+) CD3(int) cells suppressed the IL-4 mRNA expression. These results suggest that NKT cells may be the cells responsible for suppression of protective immunity against T. gondii infection by interfering with the gamma delta T cell-induced HSP65 expression, possibly through the generation of IL-4.
authors.affiliation: Department of Parasitology and Immunology, School of Medicine, The University of Tokushima, Tokushima, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Hajime
authors.initials: H
authors.lastname: Hisaeda
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Manxin
authors.initials: M
authors.lastname: Zhang
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Tianqian
authors.initials: T
authors.lastname: Zhang
authors.forename: Miwa
authors.initials: M
authors.lastname: Takashima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nishitani
authors.forename: Robert A
authors.initials: RA
authors.lastname: Good
authors.forename: Kunisuke
authors.initials: K
authors.lastname: Himeno
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000378:metabolism*; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*
chemical_list: D000906:Antibodies; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; C074119:heat-shock protein 65, Mycobacterium; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma; D018833:Chaperonins