Defective development of NK1.1+ T-cell antigen receptor αβ+ cells in zeta-associated protein 70 null mice with an accumulation of NK1.1+CD3− NK-like cells in the thymus

Iwabuchi, Kazuya; Iwabuchi, Chikako; Tone, Saori; Itoh, Daisuke; Tosa, Noriko; Negishi, Izumi; Ogasawara, Kunio; Uede, Toshimitsu; Onoé, Kazunori

doi:10.1182/blood.v97.6.1765

Cited by 36 publications

(24 citation statements)

References 54 publications

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“…1). This supports previous published data (22,29) and explains why some reports, including our own, suggested that NKT cells are DX5 Ϫ/low , because these reports typically used the FITC-conjugated reagent (23)(24)(25)(26)(27). PE-conjugated anti-CD49b demonstrated that virtually all NKT cells are CD49b ϩ (Fig.…”

Section: A Comparison Of Different Dx5/cd49b Reagentssupporting

confidence: 78%

“…The results in this study help to shed light on this problem, showing a large degree of variability with different Abs specific for DX5/CD49b. The increased efficiency of labeling with PE-conjugated reagents reveals that nearly all CD1d-dependent NKT cells express CD49b, in contrast to the conclusions made in some earlier studies, including our own (23)(24)(25)(26)(27). However, it is also clear that CD49b is expressed by many more T cells than can be accounted for by CD1d-dependent NKT cells, and most CD49b ϩ T cells are not classical NKT cells (4), although they are potent cytokine-producing cells in their own right, and are clearly heterogeneous for a range of surface markers, including CD4, CD8, NK1.1, CD62L, CD69, and CD25.…”

Section: Discussioncontrasting

confidence: 55%

“…Because the T cells defined by DX5 were of a similar low frequency to NKT cells, showed at least partial overlap with NK1.1 ϩ T cells, produced high levels of cytokines, and appeared to exhibit immunoregulatory capabilities, this marker has, and continues to be, used as a surrogate marker for NKT cells (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The use of DX5 to define NKT cells was challenged when some groups published that CD1d-dependent NKT cells were either negative or very low for expression of this marker (23)(24)(25)(26)(27)(28). However, new evidence has emerged supporting the usefulness of DX5 as a means for defining NKT cells, demonstrating that CD1d-dependent NKT cells are labeled with DX5 if the more sensitive, PE-conjugated Ab is used (22,29).…”

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confidence: 99%

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DX5/CD49b-Positive T Cells Are Not Synonymous with CD1d-Dependent NKT Cells

Pellicci

Hammond

Coquet

et al. 2005

The Journal of Immunology

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NKT cells are typically defined as CD1d-dependent T cells that carry an invariant TCR α-chain and produce high levels of cytokines. Traditionally, these cells were defined as NK1.1+ T cells, although only a few mouse strains express the NK1.1 molecule. A popular alternative marker for NKT cells has been DX5, an Ab that detects the CD49b integrin, expressed by most NK cells and a subset of T cells that resemble NKT cells. Interpretation of studies using DX5 as an NKT cell marker depends on how well DX5 defines NKT cells. Using a range of DX5 and other anti-CD49b Abs, we reveal major differences in reactivity depending on which Ab and which fluorochrome are used. The brightest, PE-conjugated reagents revealed that while most CD1d-dependent NKT cells expressed CD49b, they represented only a minority of CD49b+ T cells. Furthermore, CD49b+ T cell numbers were near normal in CD1d−/− mice that are completely deficient for NKT cells. CD1d tetramer− CD49b+ T cells differ from NKT cells by their activation and memory marker expression, tissue distribution, and CD4/CD8 coreceptor profile. Interestingly, both NKT cells and CD1d tetramer− CD49b+ T cells produce cytokines, but the latter are clearly biased toward Th1-type cytokines, in contrast to NKT cells that produce both Th1 and Th2 cytokines. Finally, we demonstrate that expression of CD49b by NKT cells does not dramatically alter with age, contrasting with earlier reports proposing DX5 as a maturation marker for NKT cells. In summary, our data demonstrate that DX5/CD49b is a poor marker for identifying CD1d-dependent NKT cells.

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Section: A Comparison Of Different Dx5/cd49b Reagentssupporting

confidence: 78%

Section: Discussioncontrasting

confidence: 55%

mentioning

confidence: 99%

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DX5/CD49b-Positive T Cells Are Not Synonymous with CD1d-Dependent NKT Cells

Pellicci

Hammond

Coquet

et al. 2005

The Journal of Immunology

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“…RNA extraction and reverse transcription-polymerase chain reaction (RT-PCR) were performed as described previously. 38 …”

Section: Rt-pcrmentioning

confidence: 99%

“…Propidium iodide (Sigma) positive cells were electronically gated out from the analysis, and stained cells were analyzed using a FACSCalibur flow cytometer, as described elsewhere. 38 In vitro culture of splenocytes from AD-or chow-fed WT mice treated with ␣-GalCer Splenocytes were obtained from either AD-or chow-fed WT mice 2 to 12 hours after intravenous injection with 0.1 g/g BW ␣-GalCer. Cells were suspended in RPMI 1640 supplemented with 10% fetal calf serum, 100 U/mL penicillin, 100 g/mL streptomycin, and 5 ϫ 10 Ϫ5 M 2-mercaptoethanol (culture medium) and were cultured in 24-well plates at 5 ϫ 10 6 /mL for 1.5 hours without additional stimulation.…”

Section: Flow Cytometrymentioning

confidence: 99%

Natural killer T cells accelerate atherogenesis in mice

Nakai

Iwabuchi²,

Fujii³

et al. 2004

Blood

177

157

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In addition, repeated injections of ␣-GalCer or the related glycolipid OCH to apolipoprotein E knockout (apoE ؊/؊ ) mice during the early phase of atherosclerosis significantly enlarged the lesion areas compared with mice injected with vehicle control. However, administering ␣-GalCer to apoE ؊/؊ mice with established lesions did not significantly increase the lesion area but considerably decreased the collagen content. Atherosclerosis development in either AD-fed WT or apoE ؊/؊ mice was associated with the presence of V␣14J␣18 transcripts in the atherosclerotic arterial walls, indicating that NKT cells were recruited to these lesions. Thioglycolate-elicited macrophages pulsed with oxidized low-density lipoproteins expressed enhanced CD1d levels and induced NKT cells to produce interferon-␥, a potentially proatherogenic T-helper 1 (T H 1) cytokine. Collectively, we conclude that NKT cells are proatherogenic in mice. IntroductionAtherosclerosis is an inflammatory vascular disease that involves components of the innate and acquired immune systems. [1][2][3] Several studies have suggested that lymphocytes, which are detected in atherosclerotic lesions in humans and mice, 4,5 play a proatherogenic role. [6][7][8] Recently, the role of distinct lymphocyte subsets in the development of atherosclerosis has been evaluated. For example, emerging evidence indicates that T-helper 1 (T H 1) cells are proatherogenic, 9 whereas T H 2 cells are antiatherogenic. 10,11 These observations are further supported by the finding that T H 1 cytokines (eg,) are important in the progression of atherosclerosis [12][13][14][15] and that, among T H 2 cytokines, IL-10 is antiatherogenic. 16 On the other hand, recent studies have suggested that B cells play a protective role in atherogenesis. 17,18 Natural killer T (NKT) cells are a unique subset of lymphocytes that have surface markers and functions of T cells and NK cells. [19][20][21][22][23] Several characteristics of NKT cells suggest that they may play a role in the atherogenic process. Most NKT cells express an invariant V␣14J␣18 T-cell receptor (TCR)-V␣ chain paired with a restricted set of TCR-V␤ chains. These classical NKT cells recognize lipid antigens presented by the major histocompatibility complex (MHC) class 1-like molecule CD1d, produce copious amounts of IFN-␥ and IL-4 on activation, 22 and constitutively express Fas-ligand. 23 Moreover, NKT cells play a protective role in several autoimmune diseases, infections, and tumor progression/ metastasis. 20 Protective effects of NKT cells and their ligands in autoimmunity are largely attributed to their capacity to promote T H 2 immune responses. 24,25 However, in some situations, NKT cells can contribute to the development of T H 1 immune responses as well. 26 Therefore, it was difficult to predict whether NKT cells would play a proatherogenic or an antiatherogenic role. 2 To date, few studies have investigated the role of CD1d and CD1d-dependent T cells in atherogenesis. CD1d-expressing cells are present in human atherosclerotic...

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

Ohwatari

Iwabuchi

et al. 2001

Cellular Immunology

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Defective development of NK1.1+ T-cell antigen receptor αβ+ cells in zeta-associated protein 70 null mice with an accumulation of NK1.1+CD3− NK-like cells in the thymus

Cited by 36 publications

References 54 publications

DX5/CD49b-Positive T Cells Are Not Synonymous with CD1d-Dependent NKT Cells

DX5/CD49b-Positive T Cells Are Not Synonymous with CD1d-Dependent NKT Cells

Natural killer T cells accelerate atherogenesis in mice

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

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