Functionally distinct NKT cell subsets and subtypes

Seino, Ken‐ichiro; Taniguchi, Masaru

doi:10.1084/jem.20051600

Cited by 108 publications

(106 citation statements)

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“…50 Therefore, the decreased frequency of iNKT cells in patients with HAM/TSP and ATL may underlie not only insufficient infected cell control but also the pathogenesis of ATL and HAM/TSP. Currently, evidence is accumulating about the potential use of iNKT-mediated immunotherapy as a clinical modulator in cancer and autoimmune disorders.…”

Section: Discussionmentioning

confidence: 99%

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Azakami

Sato

Araya

et al. 2009

Blood

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Invariant natural killer T (iNKT) cells are unique T cells that regulate the immune response to microbes, cancers, and autoimmunity. We assessed the characteristics of iNKT cells from persons infected with human T-lymphotropic virus type 1 (HTLV-1). Whereas most infected persons remain asymptomatic carriers (ACs IntroductionHuman T-cell lymphotropic virus type 1 (HTLV-1) causes persistent infection. Whereas most infected persons remain asymptomatic carriers (ACs), 3% to 5% develop a T-cell malignancy termed adult T-cell leukemia (ATL), and another 0.25% to 3% develop a chronic progressive inflammatory neurologic disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/ TSP). [1][2][3] One of the most important pathogenic factors in HAM/ TSP is an increased HTLV-1 load in the peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid, 4-6 which suggests that in affected persons, virus control is inadequate. A higher HTLV-1 load increases the risk of HAM/TSP and ATL. 4,7 Therefore, the precise mechanisms controlling HTLV-1-infected cells must be better understood. With regard to the host defense mechanisms involved in HTLV-1 infection, the role of HTLV-1-specific CD8 ϩ cytotoxic T lymphocytes (CTLs) has been studied. [8][9][10] The HTLV-1-specific CTL response is critical for a low viral load to be maintained. [9][10][11] Despite the high frequency of HTLV-1-specific CTLs, the number of HTLV-1-infected T cells is surprisingly high in HAM/TSP patients. 5,6 We and others have reported that the maturation and functioning of HTLV-1-specific CTLs are inadequate in HAM/TSP patients, although in vitro studies have shown that these CTLs exert cytolytic activity against HTLV-1-expressing target cells. 12,13 Therefore, we hypothesize that there may be another cell population without CTLs that contributes to the control of HTLV-1-infected T cells.A unique T-cell subpopulation, natural killer T (NKT) cells, constitute a subset of lymphocytes that share the features of both innate and adaptive immune cells. Unlike conventional T cells, NKT cells express a T-cell receptor (TCR) that recognizes glycolipids instead of protein antigens. Moreover, these cells share properties and receptors with NK cells. They rapidly produce granzymes and perforins on stimulation. Among the CD3 ϩ T cells in human blood, 10% to 25% express NK cell-surface molecules, such as CD161, and these can be classified as NKT cells. 14,15 A small population of T cells within this NKT cell subset expresses a highly conserved V␣24J␣18 TCR chain that associates preferentially with V␤11. [16][17][18] These T cells are referred to as invariant NKT (iNKT) cells. Very recently, a novel clonotypic monoclonal antibody 6B11 specific for the V␣24J␣18 TCR chain has been shown to selectively stain human iNKT cells. 18,19 Activation of human iNKT cells requires the presentation of glycolipids, such as ␣-galactosylceramide (␣-GalCer) on the major histocompatibility complex class I-like molecule CD1d. 20 ␣-GalCer stimulation induces rapid cytoki...

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Section: Discussionmentioning

confidence: 99%

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Azakami

Sato

Araya

et al. 2009

Blood

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“…This is supported by the observation in our hospital that patients who did not receive SCT after consolidation chemotherapy frequently relapsed within one year, and were unable to achieve CR with subsequent chemotherapy, developing refractory leukemia. Le Dieu et al 16 showed that CD3 + CD56 + T lymphocytes are not true NKT cells, though a review of the literature [17][18][19][20][21] suggested that CD3 + CD56 + T lymphocytes may include several subsets, including NKT and cytokine-induced killer cells (CIK). increased in AL compared with healthy controls, they were unable to prevent disease progression.…”

Section: Numbers Of Cd3mentioning

confidence: 99%

Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

Guo

Chen

Dong

et al. 2013

Cancer Biology & Therapy

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“…A tolerogenic role has also been recently described for fractalkine (CX3CR1) since knockout mice failed to develop oral tolerance [18]. Invariant Vα24 restricted T cells (iNKT cells) also play a role in oral tolerance although their exact role remains unclear [19][20][21].In healthy individuals, gut microenvironment controls the phenotype and function of human DCs. Thus, tolerogenic "gutlike" DCs can be generated when they are exposed to such microenvironments [22][23][24][25][26].…”

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IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

et al. 2012

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Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL-13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls. Levels of IL-13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a Th2 cytokine profile. IL-6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the Mayo endoscopic score for severity of disease. DCs conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DCs conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin-homing chemokine CCR8. These DCs did not have decreased T-cell stimulatory capacity and primed T cells with the skin-homing CLA molecule in an IL-6-dependent mechanism. Our results highlight the role of IL-6 in UC and question the concept of UC as a Th2 disease and the relevance of IL-13 in its etiology.Keywords: Dendritic cells r IL-6 r Mucosal immunity r Intestinal immunity r Ulcerative colitis Correspondence: Prof. Stella C. Knight e-mail: s.knight@imperial.ac.uk IntroductionThe gastrointestinal tract is in contact with a wide variety of commensal microbiota and diverse pathogens, and therefore C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 1338 David Bernardo et al. Eur. J. Immunol. 2012. 42: 1337-1353 requires a balance to be maintained between immunity and immune tolerance; the lack of immune responses against food antigens and/or the commensal microbiota is essential to maintain the homeostasis of the gastrointestinal tract [1]. Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), traditionally related to a Th2 cytokine profile mediated by 3], where immune homeostasis of the gastrointestinal tract is compromised. Up to 1/3rd of UC patients can develop extraintestinal manifestations with the skin being one of such tissues [4,5].Dendritic cells (DCs) are the most potent antigen presenting cells and determine the nature and type of immune responses [6,7]. Intestinal DCs control immune tolerance in the gastrointestinal tract [8][9][10]. DCs also maintain immune responses localized to specific tissues, since they imprint specific tissue-homing profiles on stimulated T cells [11]. Retinoic acid (RA), the active form of vitamin A following dehydrogenization by the RALDH2 enzyme controls some of the mechanisms of immune homeostasis of the gut [12][13][14]. RA-producing DCs mediate the IgA switching of B cells [15], the generation of T cells with a regulatory phenotype [10], and the imprinting of gut-homing markers on B and T cells [16,17], thereby keeping tolerogenic immune responses com...

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Functionally distinct NKT cell subsets and subtypes

Cited by 108 publications

References 30 publications

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

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Functionally distinct NKT cell subsets and subtypes

Cited by 108 publications

References 30 publications

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Numbers and cytotoxicities of CD3+CD56+T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

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Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia