Predominant expression of invariant Vα14+ TCR α chain in NK1.1+ T cell populations

Makino, Yuko; Kanno, Rieko; Ito, Toshihiro; Higashino, Kazuko; Taniguchi, Masaru

doi:10.1093/intimm/7.7.1157

Cited by 230 publications

(172 citation statements)

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“…The majority of CD1d-reactive NK T cells in the spleen are V␣14 ϩ NK T cells that express a single invariant TCR␣-chain encoded by the V␣14J␣281 segment (21)(22)(23). J␣281 KO mice show marked reduction in total NK T cells in multiple organs (24) and, while lacking V␣14 NK T cells, express CD1d molecules.…”

Section: Deficit In Il-10 Production Correlates With Failure Of J␣281mentioning

confidence: 99%

NK T Cell-Derived IL-10 Is Essential for the Differentiation of Antigen-Specific T Regulatory Cells in Systemic Tolerance

Sonoda

Faunce

Taniguchi

et al. 2001

The Journal of Immunology

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In a model of systemic tolerance called Anterior Chamber-Associated Immune Deviation (ACAID), the differentiation of the T regulatory (Tr) cells depends on NK T cells and occurs in the spleen. We now show that the CD1d-reactive NK T cell subpopulation, required for development of systemic tolerance, expresses the invariant Vα14Jα281 TCR because Jα281 knockout (KO) mice were unable to generate Ag-specific Tr cells and ACAID. The mechanism for NK T cell-dependent differentiation of Ag-specific Tr cells mediating systemic tolerance was studied by defining the cytokine profiles in heterogeneous and enriched NK T spleen cells. In contrast to there being no differences in most regulatory cytokine mRNAs, both mRNA and protein for IL-10 were increased in splenic NK T cells of anterior chamber (a.c.)-inoculated mice. However, IL-10 mRNA was not increased in spleens after i.v. inoculation. Finally, NK T cells from wild-type (WT) mice, but not from IL-10 KO mice, reconstituted the ACAID inducing ability in Jα281 KO mice. Thus, NK T cell-derived IL-10 is critical for the generation of the Ag-specific Tr cells and systemic tolerance induced to eye-inoculated Ags.

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Section: Deficit In Il-10 Production Correlates With Failure Of J␣281mentioning

confidence: 99%

NK T Cell-Derived IL-10 Is Essential for the Differentiation of Antigen-Specific T Regulatory Cells in Systemic Tolerance

Sonoda

Faunce

Taniguchi

et al. 2001

The Journal of Immunology

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219

168

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“…A remarkable property of NKT cells is their ability to rapidly produce Th1 and Th2 cytokines, such as IFN-c and IL-4, after activation [1]. The largest and best-studied fraction of murine NKT cells carries an invariant Va14-to-Ja18 TCR rearrangement (Va14i) that recognizes glycolipid struc-tures in the context of CD1d [3][4][5]. Depending on the organ investigated, most of these invariant Va14 + NKT (iNKT) cells express CD4 [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Immediate antigen‐specific effector functions byTCR‐transgenic CD8⁺ NKT cells

Wingender¹,

Berg²,

Jüngerkes³

et al. 2006

Eur J Immunol

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Only recently have natural antigens for CD1d-dependent, invariant Va14 + natural killer T (iNKT) cells been identified. Similar data for CD1d-independent and CD8 + NKT cell populations are still missing. Here, we show that the MHC class I-restricted CD8 + TCRtransgenic mouse lines OT-I, P14 and H-Y contain a significant proportion of transgenic CD8 + NK1.1 + T cells. In liver, most of NK1.1 + T cells express CD8aa homodimers. Transgenic NKT cells did not bind invariant Va14-to-Ja18 TCR rearrangement (Va14i)-specific CD1d/a-galactosylceramide tetramers and the frequency of iNKT cells was severely reduced. The activated cell surface phenotype and the distribution of transgenic NKT cells in vivo were similar to that reported for iNKT cells. The OT-I and P14 CD8 + NKT cells recognized their cognate antigen in the context of H2-K b and produced cytokines shortly after TCR stimulation. Importantly, transgenic NKT cells exerted immediate antigen-specific cytotoxicity in vitro and in vivo. Our results demonstrate the presence of transgenic CD8 + NKT cells in MHC class I-restricted TCR-transgenic animals, which are endowed with rapid antigen-specific effector functions. These data imply that experiments studying naive T cell function in TCR-transgenic animals should be interpreted with caution, and that such animals could be utilized for studying CD8 + NKT cell function in an antigen-specific manner.

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“…[1][2][3] V␣14 NKT cells recognize a glycolipid, ␣-GalCer, in a CD1d-depenent fashion. 4 The CD1d molecule has been well conserved throughout mammalian evolution and lacks allelic polymorphism.…”

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confidence: 99%

Preserved IFN‐α production of circulating Vα24 NKT cells in primary lung cancer patients

Motohashi

Kobayashi

Ito

et al. 2002

Intl Journal of Cancer

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Human V␣24 NKT cells bearing an invariant V␣24J␣Q antigen receptor, the counterpart of murine V␣14 NKT cells, are activated by a specific ligand, ␣-GalCer, in a CD1d-dependent manner. Here, we demonstrate decreased numbers of circulating V␣24 NKT cells in patients with primary lung cancer compared to healthy volunteers. However, V␣24 NKT cells and DCs from lung cancer patients were functionally normal, even in the presence of tumor. Furthermore, levels of V␣24 NKT cells in surgically resected lung tissue appeared to be equivalent to those of V␣14 NKT cells in the mouse lung. Levels of V␣24 NKT cells in the tumor tissue itself were increased about 2.5 times. Administration of ␣-GalCer-pulsed DCs expanded V␣14 NKT cells in the lung more than 10 times, and the increased levels were sustained for 1 week. This may explain the previous finding that ␣-GalCer-pulsed DCs exerted strong antitumor activity in mouse lung tumor metastatic models. The potential use of ␣-GalCer-pulsed DCs for immunotherapy aimed at activating endogenous V␣24 NKT cells in the lung of cancer patients is discussed. © 2002 Wiley-Liss, Inc. Key words: V␣24 NKT cell; IFN-␥ primary lung cancer; ␣-galactosylceramide; single-cell sorting RT-PCRMurine V␣14 NKT cells are characterized by coexpression of NK1.1, an NK cell marker, and an invariant antigen receptor encoded by V␣14 and J␣281 gene segments. 1-3 V␣14 NKT cells recognize a glycolipid, ␣-GalCer, in a CD1d-depenent fashion. 4 The CD1d molecule has been well conserved throughout mammalian evolution and lacks allelic polymorphism. 5-7 After activation, V␣14 NKT cells inhibit tumor metastasis in certain experimental animal models. 8 -10 Furthermore, i.v. injection of ␣-GalCer-pulsed DCs expressed a potent antitumor effect in a B16 melanoma liver metastasis model, where metastasized tumor nodules were eradicated. 11 Human NKT cells bearing the invariant V␣24J␣Q receptor are considered to be the counterpart of murine V␣14 NKT cells and may recognize antigens similar to those of murine V␣14 NKT cells because of striking homology between human V␣24 and mouse V␣14 receptors, particularly in their complementarity-determining region 3. 2 Indeed, human V␣24 NKT cells were activated by ␣-GalCer in a CD1d-dependent fashion 5,12,13 and showed strong antitumor activity upon ␣-GalCer stimulation. 14,15 Human V␣24 NKT cells play crucial roles in various immune responses, including antitumor and autoimmune responses. 16 -19 These reports demonstrated selective reduction in V␣24 NKT cell numbers. Little is known, however, about the nature of V␣24 NKT cells in primary lung cancer patients.We investigated the function of V␣24 NKT cells in peripheral blood and lung of patients with lung cancer. The numbers of V␣24 NKT cells were reduced, whereas the function of freshly isolated V␣24 NKT cells appeared to be preserved in tumor-bearing patients. Furthermore, the ability to present ␣-GalCer by patient DCs was within a normal range. Administration of ␣-GalCer-pulsed DCs expanded V␣14 NKT cells in the lung more than 10 ti...

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Predominant expression of invariant V_α14⁺ TCR α chain in NK1.1⁺ T cell populations

Cited by 230 publications

References 0 publications

NK T Cell-Derived IL-10 Is Essential for the Differentiation of Antigen-Specific T Regulatory Cells in Systemic Tolerance

NK T Cell-Derived IL-10 Is Essential for the Differentiation of Antigen-Specific T Regulatory Cells in Systemic Tolerance

Immediate antigen‐specific effector functions byTCR‐transgenic CD8⁺ NKT cells

Preserved IFN‐α production of circulating Vα24 NKT cells in primary lung cancer patients

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Predominant expression of invariant Vα14+ TCR α chain in NK1.1+ T cell populations

Cited by 230 publications

References 0 publications

NK T Cell-Derived IL-10 Is Essential for the Differentiation of Antigen-Specific T Regulatory Cells in Systemic Tolerance

NK T Cell-Derived IL-10 Is Essential for the Differentiation of Antigen-Specific T Regulatory Cells in Systemic Tolerance

Immediate antigen‐specific effector functions byTCR‐transgenic CD8+ NKT cells

Preserved IFN‐α production of circulating Vα24 NKT cells in primary lung cancer patients

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Product

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Predominant expression of invariant V_α14⁺ TCR α chain in NK1.1⁺ T cell populations

Immediate antigen‐specific effector functions byTCR‐transgenic CD8⁺ NKT cells