Invariant natural killer T cells from rhesus macaque spleen and peripheral blood are phenotypically and functionally distinct populations

Balgansuren, Gansuvd; Goodwin, Jeanine; Asiedu, Clement; Jiang, Xiao Ling; Jargal, Uuganbayar; Andrades, Patricio; Exley, Mark A.; Thomas, Judith M.

doi:10.1111/j.1600-0684.2007.00222.x

Cited by 14 publications

(21 citation statements)

References 63 publications

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“…2A). Consistent with some previous reports of studies using rhesus macaques (14,20), very few NKT cells in the animals tested carried the CD4 Ϫ CD8 Ϫ phenotype that is common for mice and humans.…”

Section: Resultssupporting

confidence: 79%

“…It was possible that spleen-derived NKT cells examined in the latter study (27) are different from blood-derived NKT cells. A recent study (14) directly compared rhesus macaque blood and spleen-derived NKT cells and found that most spleen NKT cells were CD4 ϩ CD8 ϩ , compared to blood, where most NKT cells were CD4 Ϫ CD8 ϩ , although even in blood, 20% were reported to be CD4 ϩ CD8 ϩ . Our results are not exactly consistent with any of the previous studies, but this may be due to the fact that we have used pigtailed macaques versus the use of rhesus macaques in all previous studies.…”

Section: Vol 83 2009 Nkt Cells In Siv-positive Macaques 1621mentioning

confidence: 99%

“…SIV and SHIV viruses, like HIV-1 strains, vary in their uses of either CXCR4 or CCR5 chemokines to enter CD4-bearing cells. There have been only a limited number of studies of NKT cells in macaques (14,15,20,27), often studying NKT cells within lymphoid organs such as the spleen. We undertook a comprehensive kinetic study of NKT cells in pigtail macaques using an ␣-galactosylceramide (␣-GalCer)-loaded CD1d tetramer prior to, and throughout, both CCR5-using SIV mac251 infection and CXCR4-using SHIV mn229 infection.…”

mentioning

confidence: 99%

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Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques

Fernandez

Chan

Kyparissoudis

et al. 2009

J Virol

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Natural killer T (NKT) cells are important regulators of immunity for infectious diseases, tumor surveillance, allergy, and autoimmunity (2,17,36). NKT cells have a semi-invariant T-cell receptor consisting of an invariant T-cell receptor ␣ (TCR-␣) chain (V␣14-Ja18 in mice and Va24-Ja18 in humans), paired with a limited array of TCR-␤ chains (comprised of V␤8.2, V␤7, or V␤2 in mice and V␤11 in humans), that facilitates the recognition of lipid-based antigens presented by the major histocompatibility complex-like molecule CD1d. NKT cells are a potent source of cytokines and facilitate several aspects of adaptive immunity in both mice and humans.

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Section: Resultssupporting

confidence: 79%

Section: Vol 83 2009 Nkt Cells In Siv-positive Macaques 1621mentioning

confidence: 99%

mentioning

confidence: 99%

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Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques

Fernandez

Chan

Kyparissoudis

et al. 2009

J Virol

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“…The specificity of 6B11 was defined by binding to the cyclic peptide used as antigen, reactivity with Jurkat cells transfected to express the iNKT TCR, reactivity to T cells derived from a mouse that expressed a human invariant AV24AJ18 TCR a-chain, and selection for and activation of iNKT clones and lines in vitro. Although raised in CD1d KO mice, 6B11 did not react with murine iNKT (or other murine) cells (data not shown), but does react with iNKT cells of rhesus macaques, non-human primates [37]. To our knowledge, this antibody is the only anti-CDR3 idiotype-specific mAb available for a TCR of known specificity.…”

mentioning

confidence: 88%

“…Hybridomas secreting antibodies reactive with invariant peptide were screened for reactivity against the DN2.D6 and other iNKT clones and for reactivity against control unrelated T cell clones by indirect immuno-staining with anti-IgG FITC as described [2,32,37]. Briefly, T cells were suspended in FACS buffer (PBS, 1% FBS and 0.1% NaN 3 ) in a 96-well plate.…”

Section: Screening For Invariant Tcr-reactive Antibodiesmentioning

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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Conservation of molecular and cellular phenotypes of invariant NKT cells between humans and non-human primates

Wilburn

Hackney

et al. 2019

Immunogenetics

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Invariant NKT (iNKT) cells in both humans and non-human primates are activated by the glycolipid antigen, α-galactosylceramide (α-GalCer). However, the extent to which the molecular mechanisms of antigen recognition and in vivo phenotypes of iNKT cells are conserved among primate species has not been determined. Using an evolutionary genetic approach, we found a lack of diversifying selection in CD1 genes over 45 million years of evolution, which stands in stark contrast to the history of the MHC system for presenting peptide antigens to T cells. The invariant T cell receptor (TCR)-α chain was strictly conserved across all seven primate clades. Invariant NKT cells from rhesus macaques ( Macaca mulatta ) bind human CD1D-α-GalCer tetramer and are activated by α-GalCer-loaded human CD1D transfectants. The dominant TCR-β chain cloned from a rhesus-derived iNKT cell line is nearly identical to that found in the human iNKT TCR, and transduction of the rhesus iNKT TCR into human Jurkat cells show that it is sufficient for binding human CD1D-α-GalCer tetramer. Finally, we used a 20-color flow cytometry panel to probe tissue phenotypes of iNKT cells in a cohort of rhesus macaques. We discovered several tissue-resident iNKT populations that have not been previously described in non-human primates but are known in humans, such as TCR-γδ iNKTs. These data reveal a diversity of iNKT cell phenotypes despite convergent evolution of the genes required for lipid antigen presentation and recognition in humans and non-human primates. Electronic supplementary material The online version of this article (10.1007/s00251-019-01118-9) contains supplementary material, which is available to authorized users.

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Invariant natural killer T cells from rhesus macaque spleen and peripheral blood are phenotypically and functionally distinct populations

Abstract: Spleen iNKT cells in rhesus macaques are Th2 biased and display phenotypically and functionally distinct profiles from their PB counterpart.

Cited by 14 publications

References 63 publications

Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques

Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques

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

Conservation of molecular and cellular phenotypes of invariant NKT cells between humans and non-human primates

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