CD1d-Restricted NKT Cells Express a Chemokine Receptor Profile Indicative of Th1-Type Inflammatory Homing Cells

Thomas, Seddon Y.; Hou, Runhua; Boyson, Jonathan E.; Means, Terry K.; Hess, Christoph; Olson, Douglas P.; Strominger, Jack L.; Brenner, Michael B.; Gumperz, Jenny E.; Wilson, S. Brian; Luster, Andrew D.

doi:10.4049/jimmunol.171.5.2571

Cited by 202 publications

(198 citation statements)

References 36 publications

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“…In human blood, NKT cells can be clearly identified using a staining combination of anti-Va24 (or 6B11 mAb, which recognizes the CDR3 a-chain loop of Va24 [23]) and anti-Vb11, or by staining with a-galactosylceramide (aGC)-loaded CD1d tetramer in combination with anti-CD3 or anti-ab-TCR. As with most instances of flow cytometry, the putative NKT cell region can include some autofluorescent, or non-specifically stained cells, but the frequency of NKT cells is usually sufficiently high to make this level of 'contamination' inconsequential to analysis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples

et al. 2005

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NKT cells are a CD1d-restricted T cell subset with strong immunoregulatory properties. Human NKT deficiencies are associated with autoimmune diseases such as type 1 diabetes and several types of cancer, yet there is little understanding of how the human NKT cell pool develops or is maintained. In this study, we present the first detailed analysis of human NKT cells from donor-matched postnatal thymus and blood samples. In mice, NKT cells are a thymus-dependent population that migrates to the periphery at an immature stage. Our data show that human NKT cells also undergo early stages of development in the thymus, forming a CD4 + CD161 -/low population that predominates neonatal thymic and blood NKT cell pools. CD4 -and CD161 + NKT cells accumulate with age in the blood, but not thymus, to the point that they dominate the NKT cell compartment in adult blood. This is consistent with the post-thymic maturation of NKT cells exported from the thymus at the putatively immature CD4 + CD161 -/low stage. Interestingly, while thymus and peripheral NKT cell frequencies vary widely between patients and are relatively stable between age groups, there is no clear relationship between the NKT cell frequency in thymus and blood.

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Section: Resultsmentioning

confidence: 99%

Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples

et al. 2005

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“…Firststrand complementary DNA (cDNA) was synthesized using oligo(dT) [12][13][14][15][16][17][18] primers (Amersham Pharmacia Biotech, Piscat-away, NJ) and SuperScript II reverse transcriptase (Invitrogen). The amount of cDNA for amplification was adjusted to the amount of RNA measured by optical density meter as well as ␤-actin polymerase chain reaction (PCR) products, using serially diluted cDNA.…”

Section: Methodsmentioning

confidence: 99%

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Nanki¹,

Shimaoka²,

Hayashida³

et al. 2005

Arthritis & Rheumatism

137

114

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Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with massive T cell infiltration into the synovium. The accumulated T cells express type 1 cytokines, such as interferon-␥ (IFN␥) and tumor necrosis factor ␣, and activated markers of inflammation, such as CD154 and inducible costimulator (ICOS). It is thought that chemokines contribute to T cell accumulation in the synovium. In this study, we examined the role of CXCL16 and CXCR6 in T cell migration and stimulation in RA synovium.Methods. Expression of CXCL16 and CXCR6 was analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction, Western blotting, and/or flow cytometry. Migration activity was assessed using a chemotaxis chamber. IFN␥ production was analyzed by enzyme-linked immunosorbent assay. The effect of anti-CXCL16 monoclonal antibody on murine collagen-induced arthritis (CIA) was evaluated.Results. CXCL16 was expressed in RA synovium.

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“…Other mAb, including anti-CD3-Cych, anti-CD161-PE, anti-CD4-Cych, were all obtained from BD-PharMingen (LaJolla, CA). Alexafluor488-labeled human CD1d tetramers were generated and used as described [4,52,53]. The TCR-negative Jurkat subline was transfected to transiently express iNKT Va24Ja18 and Vb11 TCR, as previously described [31].…”

mentioning

confidence: 99%

Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR α‐chain CDR3 loop

Exley¹,

Hou²,

Shaulov³

et al. 2008

Eur J Immunol

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A significant fraction of CD1d-restricted T cells express an invariant T cell receptor (TCR) a-chain. These highly conserved invariant NKT (iNKT) populations are important regulators of a wide spectrum of immune responses. The ability to directly identify and manipulate iNKT cells is essential to understanding their function and to exploit their therapeutic potential. To this end, we sought monoclonal and polyclonal antibodies specific for iNKT cells by immunizing CD1d KO mice, which lack iNKT cells, with a cyclic peptide modeled after the TCRa CDR3 loop. One mAb (6B11) was specific for cloned and primary human but not rodent iNKT cells and the human invariant TCRa, as shown by transfection and reactivity with human invariant TCRa transgenic T cells ex vivo and in situ. 6B11 was utilized to identify, purify, and expand iNKT cells from an otherwise minor component of human peripheral blood lymphocytes and to specifically identify human iNKT cells in tissue. Thus, we report a novel and general strategy for the generation of mAb specific for the CDR3 loop encoded by the TCR of interest. Specifically, an anti-Va24Ja18 CDR3 loop clonotypic TCR mAb is available for the enumeration and therapeutic manipulation of human and non-human primate iNKT populations.Key words: Anti-TCR Á Clonotypic Á Cyclic peptide Á IL-4 Á Invariant NKT Introduction Natural killer T (NKT) cells expressing surface markers found on NK cells (e.g. CD161, CD56, CD94 and/or KIR) comprise up to 20% of human peripheral blood lymphocytes (PBL) [1], whilst only *0.05% of PBL are CD1d restricted [2][3][4]. A major proportion of such PBL CD1d-reactive T cells are invariant NKT (iNKT) cells in that they express an invariant TCR a-chain, Va24Ja18 in humans and Va24Ja18 in mice [3,5,6]. Both human and murine iNKT cells can be activated in a CD1d-dependent fashion by the synthetic glycolipid a-galactosylceramide (a-GalCer) and self-or pathogen-derived glycolipid molecules [7][8][9]. Activation of iNKT cells leads to rapid production of large amounts of numerous cytokines and consequent stimulation of Mark A. Exley et al. Eur. J. Immunol. 2008. 38: 1756-1766 [3,[10][11][12][13][14], perhaps most significantly by regulating dendritic cell (DC) function [10,15]. The frequency and functional activity of iNKT cells have been shown to be important determinants for the progression of autoimmune disorders, tumors, and viral infections [10,[16][17][18]. In humans, a reduction in the number of circulating iNKT cells is accompanied by a striking Th1 polarization in certain autoimmune diseases such as type 1 diabetes, systemic sclerosis and rheumatoid arthritis [18][19][20][21]. Cancer patients have decreased numbers of iNKT cells in their blood and impaired in vitro proliferative potential, reversible with IL-2 [22][23][24]. As well as the reduced numbers of these cells found in many cancer patients, there is a striking reversal of cytokine polarization relative to that found in diabetes, which may reflect a reduction in iNKT anti-tumor activity during progression [...

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CD1d-Restricted NKT Cells Express a Chemokine Receptor Profile Indicative of Th1-Type Inflammatory Homing Cells

Cited by 202 publications

References 36 publications

Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples

Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR α‐chain CDR3 loop

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