Cd1d–Glycolipid Tetramers

MacDonald, H. Robson

doi:10.1084/jem.192.5.f15

Cited by 37 publications

(5 citation statements)

References 30 publications

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“…These may each develop directly from CD4 + NK1.1 − population, as most CD4 + NK1.1 + NKT cells retained that phenotype following transfer. This pathway contrasts an earlier pathway proposed by MacDonald ( 51 ), based on NK1.1 + NKT cell ontogeny, suggesting that DN NKT cells develop before CD4 + NKT cells. Indeed, our data in Fig.…”

Section: Discussioncontrasting

confidence: 99%

“…4 A). Similar cells have been previously observed ( 30 ) and the possibility has been raised that they represent an early precursor stage in the NKT cell lineage ( 51 ). However, we did not detect a stage during NKT cell ontogeny at which these cells appeared to be significantly more abundant, and careful analysis of these cells showed that they appeared to be larger than other NKT cells based on forward light scatter (data not shown), suggesting that they might be doublets.…”

Section: Resultssupporting

confidence: 84%

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A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1−CD4+ CD1d-dependent Precursor Stage

Pellicci

Hammond

Uldrich

et al. 2002

The Journal of Experimental Medicine

342

398

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The development of CD1d-dependent natural killer T (NKT) cells is poorly understood. We have used both CD1d/α-galactosylceramide (CD1d/αGC) tetramers and anti-NK1.1 to investigate NKT cell development in vitro and in vivo. Confirming the thymus-dependence of these cells, we show that CD1d/αGC tetramer-binding NKT cells, including NK1.1+ and NK1.1− subsets, develop in fetal thymus organ culture (FTOC) and are completely absent in nude mice. Ontogenically, CD1d/αGC tetramer-binding NKT cells first appear in the thymus, at day 5 after birth, as CD4+CD8−NK1.1−cells. NK1.1+ NKT cells, including CD4+ and CD4−CD8− subsets, appeared at days 7–8 but remained a minor subset until at least 3 wk of age. Using intrathymic transfer experiments, CD4+NK1.1− NKT cells gave rise to NK1.1+ NKT cells (including CD4+ and CD4− subsets), but not vice-versa. This maturation step was not required for NKT cells to migrate to other tissues, as NK1.1− NKT cells were detected in liver and spleen as early as day 8 after birth, and the majority of NKT cells among recent thymic emigrants (RTE) were NK1.1−. Further elucidation of this NKT cell developmental pathway should prove to be invaluable for studying the mechanisms that regulate the development of these cells.

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Section: Discussioncontrasting

confidence: 99%

Section: Resultssupporting

confidence: 84%

A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1−CD4+ CD1d-dependent Precursor Stage

Pellicci

Hammond

Uldrich

et al. 2002

The Journal of Experimental Medicine

342

398

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“…All protocols show significant level of cell death, which corresponds to ratio of LDH by MTT [16,44]. However consequences for cell’s, cell death was higher from Protocol 1 conjugates and lowest from Protocol 3.…”

Section: Resultsmentioning

confidence: 99%

Biocompatible Gold Nanorod Conjugates for Preclinical Biomedical Research

Liopo

Conjusteau²,

Tsyboulski³

et al. 2012

J Nanomedic Nanotechnol

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Gold nanorods with a peak absorption wavelength of 760 nm were prepared using a seed-mediated method. A novel protocol has been developed to replace hexadecyltrimethylammonium bromide on the surface of the nanorods with 16-mercaptohexadecanoic acid and metoxy-poly(ethylene glycol)-thiol, and the monoclonal antibody HER2. The physical chemistry properties of the conjugates were monitored through optical and zeta-potential measurements to confirm surface chemistry changes. The efficiency of the modifications was quantified through measurement of the average number of antibodies per gold nanorod. The conjugates were investigated for different cells lines: BT-474, MCF7, MCF10, MDCK, and fibroblast. The results show successful cell accumulation of the gold nanorod HER2 conjugates in cells with HER2 overexpression. Incubation of the complexes in heparinized mouse blood demonstrated the low aggregation of the metallic particles through stability of the spectral properties, as verified by UV/VIS spectrometry. Cytotoxicity analysis with LDH release and MTT assay confirms strong targeting and retention of functional activity of the antibody after their conjugation with gold nanorods. Silver staining confirms efficient specific binding to BT-474 cells even in cases where the nanorod complexes were incubated in heparinized mouse blood. This is confirmed through in vivo studies where, following intravenous injection of gold nanorod complexes, silver staining reveals noticeably higher rates of specific binding in mouse tumors than in healthy liver. The conjugates are reproducible, have strong molecular targeting capabilities, have long term stability in vivo and can be used in pre-clinical applications. The conjugates can also be used for molecular and optoacoustic imaging, quantitative sensing of biological substrates, and photothermal therapy.

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“…Thymus-dependent NKT cells are positively selected by CD1d, a nonclassical MHC class I–like, β 2 -microglobulin-associated molecule, and they predominantly express the invariant Vα14-Jα18 TCR ( 4 – 7 ). These so-called Vα14 i NKT cells respond to the marine sponge-derived glycolipid α-galactosyl ceramide (α-GalCer) and can be identified by staining with α-GalCer–loaded CD1d tetramers ( 8 – 10 ). Other populations of NKT cells, defined by NK-1.1 and TCR expression, do not express the Vα14-Jα18 TCR and thus are unresponsive to α-GalCer ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Differential Requirement for Rel/Nuclear Factor κB Family Members in Natural Killer T Cell Development

Sivakumar

Hammond

Howells

et al. 2003

The Journal of Experimental Medicine

151

160

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Natural killer T (NKT) cells have been implicated in diverse immune responses ranging from suppression of autoimmunity to tumor rejection. Thymus-dependent NKT cells are positively selected by the major histocompatibility complex class I–like molecule CD1d, but the molecular events downstream of CD1d are still poorly understood. Here, we show that distinct members of the Rel/nuclear factor (NF)-κB family of transcription factors were required in both hematopoietic and nonhematopoietic cells for normal development of thymic NKT cells. Activation of NF-κB via the classical IκBα-regulated pathway was required in a cell autonomous manner for the transition of NK-1.1–negative precursors that express the TCR Vα14-Jα18 chain to mature NK-1.1–positive NKT cells. The Rel/NF-κB family member RelB, on the other hand, had to be expressed in radiation resistant thymic stromal cells for the generation of early NK-1.1–negative NKT precursors. Moreover, NF-κB–inducing kinase (NIK) was required for both constitutive thymic DNA binding of RelB and the specific induction of RelB complexes in vitro. Thus, distinct Rel/NF-κB family members in hematopoietic and nonhematopoietic cells regulate NKT cell development with a unique requirement for NIK-mediated activation of RelB in thymic stroma.

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Cd1d–Glycolipid Tetramers

Cited by 37 publications

References 30 publications

A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1−CD4+ CD1d-dependent Precursor Stage

A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1−CD4+ CD1d-dependent Precursor Stage

Biocompatible Gold Nanorod Conjugates for Preclinical Biomedical Research

Differential Requirement for Rel/Nuclear Factor κB Family Members in Natural Killer T Cell Development

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