Developmental and Functional Analyses of CD8+ NK1.1+ T Cells in Class-I-Restricted TCR Transgenic Mice

Ohwatari, Ryuichiro; Iwabuchi, Kazuya; Iwabuchi, Chikako; Morohashi, Taiki; Sawa, Hirofumi; Hioki, Kyoji; Kobayashi, Kimio; Fukuda, Satoshi; Inuyama, Yukio; Onoé, Kazunori

doi:10.1006/cimm.2001.1862

Cited by 6 publications

(8 citation statements)

References 49 publications

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“…While Vb5 may form a complex with the invariant Va14 TCR chain, it may not transmit a positively selecting signal. In agreement with the assumption of agonistic selection of the tgNKT cells and in accordance with previous studies [37,40,42], we show increased CD8 + tgNKT cell numbers on a negatively selecting background (H-Y TCR-transgenic male; Fig. 1, Table 1).…”

Section: Discussionsupporting

confidence: 93%

“…Therefore, we consider the NK1.1-positive population of T cells we found in TCR-transgenic animals as a genuine NKT cell population. In line with such an interpretation, other groups have reported the presence of NKT cells in CD8 + TCR-transgenic mouse lines H-Y [36,37], BM3.3 [38,39] and 2C [40], as well as in the CD4 + TCR-transgenic mouse lines DO11.10 [41] and 3BBM74 [42]. Here, we extend the list of mouse lines bearing tgNKT cells to include OT-I and P14 (Fig.…”

Section: Discussionsupporting

confidence: 76%

“…However, the mice analyzed in this study were unprimed and therefore have to be considered as antigen naive. Nonetheless, NK1.1 surface expression is probably not due to a general upregulation of NK1.1 on activated CD8 + T cells, as we never detected increased NK1.1 expression on transgenic CD8 + T cells after challenge with virally encoded antigen (ovalbumin-expressing adenovirus for OT-I) or soluble antigen (OVA 257-264 for OT-I and gp33 [33][34][35][36][37][38][39][40][41] for P14) in vitro or in vivo (data not shown). Schüler et al recently reported that thymic emigrants in neonates give rise to natural memory T cells with an activated phenotype [32], although the authors did not analyze the expression of NK1.1 on these cells.…”

Section: Discussionmentioning

confidence: 99%

“…Cytokine expression in tgNKT cells following anti-TCR Ab treatment has been reported for 2C [40] and DO11.10 [41] and antigen-specific cytotoxicity was shown for male H-Y T cells, but only after 8 days in culture with IL-2 (200 U/mL) [36]. None of these publications addressed early effector functions following antigen-specific stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…For antigen-specific stimulation, we incubated OT-I and P14 lymphocytes in vitro with OVA 257-264 or gp33 [33][34][35][36][37][38][39][40][41] peptide, respectively. In contrast to the stimulation with anti-CD3e Ab in vivo, cytokine production (IFN-c, TNF-a and IL-2) was slower and was only seen after 1.5 h of incubation.…”

Section: Nk11 + Transgenic T Cells In Mhc Class Ii-restricted Tcr-trmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Nk11 + Transgenic T Cells In Mhc Class Ii-restricted Tcr-trmentioning

confidence: 99%

See 3 more Smart Citations

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

Wingender¹,

Berg²,

Jüngerkes³

et al. 2006

Eur J Immunol

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Immunology and functional genomics of Beh�et's disease

Zierhut

Mizuki

Ohno

et al. 2003

Cellular and Molecular Life Sciences (CMLS)

121

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Behçet's disease (BD) is a multisystemic inflammatory disorder. Although the cause and pathogenesis of BD are still unclear, there is evidence for genetic, immunologic and infectious factors at the onset or in the course of BD. This review focuses on the functional genomics and immunology of BD. HLA-B51 is the major disease susceptibility gene locus in BD. An increased number of gammadelta T cells in the peripheral blood and in the involved tissues have been reported. However, the T cells at the sites of inflammation appear to be a phenotypically distinct subset. There is also a significant gammadelta T cell proliferative response to mycobacterial 65-kDa heat shock protein peptides. Homologous peptides derived from the human 60-kDa heat shock protein were observed in BD patients. There is evidence that natural killer T cells may also play a role in BD.

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Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells

et al. 2007

Self Cite

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If Th1 or Th2 polarization could be artificially manipulated, effective immune responses would be generated depending on nature of the targets. In this study we attempted to regulate CD40 expressions on dendritic cells (DCs) in order to modify the T cell response. It was found that reducing agents selectively inhibited surface expression of CD40 on DCs. This finding may provide a new strategy of DC-mediated modulation of the Th1/Th2 balance. It was also shown that NKT-produced Th1/Th2 cytokine balance was under control of negative feedback loop through DCs. Th1 cytokine-pretreated DCs mainly induced Th2 cytokine production, whereas Th2 cytokine-pretreated DCs induced Th1 cytokine production by α-galactosylceramide-stimulated NKT cells. The negative feedback regulation system could be applicable to therapeutics of various diseases based on immunological disorders.

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Developmental and Functional Analyses of CD8+ NK1.1+ T Cells in Class-I-Restricted TCR Transgenic Mice

Cited by 6 publications

References 49 publications

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

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

Immunology and functional genomics of Beh�et's disease

Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells

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Developmental and Functional Analyses of CD8+ NK1.1+ T Cells in Class-I-Restricted TCR Transgenic Mice

Cited by 6 publications

References 49 publications

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

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

Immunology and functional genomics of Beh�et's disease

Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells

Contact Info

Product

Resources

About

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

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