Vα14 natural killer T (NKT) cells produce large amounts of both IL-4 and IFN-γ upon stimulation with a ligand, α-galactosylceramide (α-GalCer), and play a crucial role in various immune responses, including allergic diseases. Interestingly, Vα14 NKT cells are not essential for the induction of IgE responses but rather induce suppression of specific IgE production upon activation. The suppression in the IgE production is not detected either in Vα14 NKT cell-deficient mice or in IFN-γ-deficient mice. Thus, activated Vα14 NKT cells are likely to exert a potent suppressive activity on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-γ. In marked contrast, little regulatory effect of IL-4 produced by Vα14 NKT cells on Th2 cell differentiation is suggested.

1.
Imai K, Kanno M, Kimoto H, Shigemoto K, Yamamoto S, Taniguchi M: Sequence and expression of transcripts of the T-cell antigen receptor α-chain gene in a functional, antigen-specific suppressor-T-cell hybridoma. Proc Natl Acad Sci USA 1986;83:8708–8712.
2.
Koseki H, Imai K, Ichikawa T, Hayata I, Taniguchi M: Predominant use of a particular α-chain in suppressor T cell hybridomas specific for keyhole limpet hemocyanin. Int Immunol 1989;1:557–564.
3.
Lantz O, Bendelac A: An invariant T cell receptor α-chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4–8– T cells in mice and humans. J Exp Med 1994;180:1097–1106.
4.
Masuda K, Makino Y, Cui J, Ito T, Tokuhisa T, Takahama Y, Koseki H, Tsuchida K, Koike T, Moriya H, Amano M, Taniguchi M: Phenotypes and invariant αβ TCR expression of peripheral Vα14+ NKT cells. J Immunol 1997;158:2076–2082.
5.
Taniguchi M, Koseki H, Tokuhisa T, Masuda K, Sato H, Kondo E, Kawano T, Cui J, Perkes A, Koyasu S, Makino Y: Essential requirement of an invariant Vα14 T cell antigen receptor expression in the development of natural killer T cells. Proc Natl Acad Sci USA 1996;93:11025–11028.
6.
Cui J, Shin T, Kawano T, Sato H, Kondo E, Toura I, Kaneko Y, Koseki H, Kanno M, Taniguchi M: Requirement for Vα14 NKT cells in IL-12-mediated rejection of tumors. Science 1997;278:1623–1626.
7.
Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, Koseki H, Taniguchi M: CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 1997;278:1626–1629.
8.
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986;136:2348–2357.
9.
Paul WE: Interleukin-4: a prototypic immunoregulatory lymphokine. Blood 1991;77:1859–1870.
10.
Yoshimoto T, Bendelac A, Hu-Li J, Paul WE: Defective IgE production by SJL mice is linked to the absence of CD4+, NK1.1+ T cells that promptly produce interleukin 4. Proc Natl Acad Sci USA 1995;92:11931–11934.
11.
Yoshimoto T, Bendelac A, Watson C, Hu-Li J, Paul WE: Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production. Science 1995;270:1845–1847.
12.
Smiley ST, Kaplan MH, Grusby MJ: Immunoglobulin E production in the absence of interleukin-4-secreting CD1-dependent cells. Science 1997;275:977–979.
13.
Brown DR, Fowell DJ, Corry DB, Wynn TA, Moskowitz NH, Cheever AW, Locksley RM, Reiner SL: β2-microglobulin-dependent NK1.1+ T cells are not essential for T helper cell 2 immune responses. J Exp Med 1996;184:1295–1304.
14.
Zhang Y, Rogers KH, Lewis DB: β2-microglobulin-dependent T cells are dispensable for allergen-induced T helper 2 responses. J Exp Med 1996;184:1507–1512.
15.
Guery JC, Galbiati F, Smiroldo S, Adorini L: Selective development of T helper (Th)2 cells induced by continuous administration of low dose soluble proteins to normal and β(2)-microglobulin-deficient BALB/c mice. J Exp Med 1996;183:485–497.
16.
Yamashita M, Kimura M, Kubo M, Shimizu C, Tada T, Perlmutter RM, Nakayama T: T cell antigen receptor-mediated activation of the Ras/mitogen-activated protein kinase pathway controls interleukin 4 receptor function and type-2 helper T cell differentiation. Proc Natl Acad Sci USA 1999;96:1024–1029.
17.
Eberl G, Lees R, Smiley ST, Taniguchi M, Grusby MJ, MacDonald HR: Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells. J Immunol 1999;162:6410–6419.
18.
Zeng D, Gazit G, Dejbakhsh-Jones S, Balk SP, Snapper S, Taniguchi M, Strober S: Heterogeneity of NK1.1+ T cells in the bone marrow: divergence from the thymus. J Immunol 1999;163:5338–5345.
19.
Hammond KJ, Pelikan SB, Crowe NY, Randle-Barrett E, Nakayama T, Taniguchi M, Smyth MJ, van Driel IR, Scollay R, Baxter AG, Godfrey DI: NKT cells are phenotypically and functionally diverse. Eur J Immunol 1999;29:3768–3781.
20.
Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H: Differential production of interferon-γ and interleukin-4 in response to Th1- and Th2-stimulating pathogens for γ δ T cells in vivo. Nature 1995;373:255–257.
21.
Zuany-Amorim C, Ruffie C, Haile S, Vargaftig BB, Pereira P, Pretolani M: Requirement for γ δ T cells in allergic airway inflammation. Science 1998;280:1265–1267.
22.
Coffman RL, Carty J: A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-γ. J Immunol 1986;136:949–954.
23.
Gajewski TF, Joyce J, Fitch FW: Antiproliferative effect of IFN-γ in immune regulation. III. Differential selection of TH1 and TH2 murine helper T lymphocyte clones using recombinant IL-2 and recombinant IFN-γ. J Immunol 1989;143:15–22.
24.
McMenamin C, Pimm C, McKersey M, Holt PG: Regulation of IgE responses to inhaled antigen in mice by antigen-specific γ δ T cells. Science 1994;265:1869–1871.
25.
Szczepanik M, Anderson LR, Ushio H, Ptak W, Owen MJ, Hayday AC, Askenase PW: γ δ T cells from tolerized αβ T cells receptor (TCR)-deficient mice inhibit contact sensitivity-effector T cells in vivo, and their interferon-γ production in vitro. J Exp Med 1996;184:2129–2139.
26.
Romagnani S: Induction of TH1 and TH2 responses: a key role for the ‘natural’ immune response? [see comments]. Immunol Today 1992,13:379–381.
27.
Kitamura H, Iwakabe K, Yahata T, Nishimura S, Ohta A, Ohmi Y, Sato M, Takeda K, Okumura K, Van Kaer L, Kawano T, Taniguchi M, Nishimura T: The natural killer T (NKT) cell ligand α-galectosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med 1999;189:1121–1128.
28.
Tomura M, Yu WG, Ahn HJ, Yamashita M, Yang YF, Ono S, Hamaoka T, Kawano T, Taniguchi M, Koezuka Y, Fujiwara H: A novel function of Vα14+ CD4+ NKT cells: stimulation of IL-12 production by antigen-presenting cells in the innate immune system. J Immunol 1999;163:93–101.
29.
Burdin N, Brossay L, Kronenberg M: Immunization with α-galactosylceramide polarizes CD1-reactive NK T cells towards Th2 cytokine synthesis. Eur J Immunol 1999;29:2014–2025.
30.
Singh N, Hong S, Scherer DC, Serizawa I, Burdin N, Kronenberg M, Koezuka Y, Van Kaer L: Cutting edge: activation of NK T cells by CD1d and α-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype. J Immunol 1999;163:2373–2377.
31.
Cui J, Watanabe N, Kawano T, Yamashita M, Kamata T, Shimizu C, Kimura M, Shimizu E, Koike J, Koseki H, Tanaka Y, Taniguchi M, Nakayama T: Inhibition of T helper cell type 2 cell differentiation and immunoglobulin E response by ligand-activated Vα14 natural killer T cells. J Exp Med 1999;190:783–792.
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