α-Galactosylceramide Induces Early B-Cell Activation through IL-4 Production by NKT Cells

Kitamura, Hiroyuki; Ohta, Akio; Sekimoto, Miho; Sato, Masamitsu; Iwakabe, Kenji; Nakui, Minoru; Yahata, Takashi; Meng, Hongxu; Koda, Toshiaki; Nishimura, Shin‐Ichiro; Kawano, Tetsu; Taniguchi, Masaru; Nishimura, Takashi

doi:10.1006/cimm.1999.1602

Cited by 126 publications

(97 citation statements)

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“…In addition, the authors observed a dichotomy of T H 1 and T H 2 differentiation dependent on whether the NKT cells were stimulated by DCs or B cells, respectively. Such findings could be reconciled with our findings, namely that MZ B cells in the mixture suffice to activate and differentiate NKT cells [34,36]. Similar findings were reported by Stockinger et al [35] for transgenic CD4 1 T cells.…”

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confidence: 93%

ICOS‐dependent stimulation of NKT cells by marginal zone B cells

et al. 2011

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Marginal zone (MZ) B cells express high levels of CD1d molecules. In accordance, MZ B cells, like splenic conventional DCs (cDCs), efficiently trigger NKT-cell proliferation. Importantly, MZ B cells exclusively induced production of IL-4 and IL-13 by such cells whereas cDCs induced robust production of mainly IFN-c. NKT-cell proliferation, IL-4 and IL-13 production induced by MZ B cells were dependent on ICOS/ICOS ligand interaction while IFN-c and IL-17 induction by cDCs required glucocorticoid-induced TNF receptor/ glucocorticoid-induced TNF receptor ligand interplay. Our data illustrate that both MZ B cells and cDCs act as efficient APCs for NKT cells and might differentially influence the quality of the subsequent immune response. IntroductionThe marginal zone (MZ) represents a unique structure in spleen that surrounds the primary follicles. It consists of a mixture of different types of cells that include macrophages, DCs, NKT cells as well as so-called MZ B cells. MZ B cells are enriched in germline-encoded specificities with low level of self-reactivity [1]. Therefore, they are maintained in a pre-activated state, which allows them to respond rapidly and T-cell independently to pathogens by antibody production. In addition, MZ B cells express high levels of the complement receptor CD21, which may enhance their response to complement coated antigens. This results in short-lived antibody responses to antigenic determinants expressed on invading viral and encapsulated bacterial species [2]. Due to their strategic location, MZ B cells, in concert with other innate cells, serve as a first line of defense against blood-borne antigens that reach the spleen [1,2]. Beyond their fast and efficient protective antibody response, MZ B cells exhibit additional important functions. They were shown to directly activate T cells and interact with APCs [1]. Moreover, MZ B cells have been shown to continuously shuttle between MZ and white pulp, which allows them to transport antigens into the follicles [3]. Remarkably, when compared to other mouse APCs, MZ B cells were found to express high levels of CD1d, the non-classical MHC I molecule responsible for presentation of lipid or glycolipid antigens to NKT cells [4][5][6][7].The major subset of CD1d-restricted murine NKT cells (invariant or type I) expresses a semi-conservative T-cell receptor (TCR) consisting of Va14-Ja18 in conjunction with Vb8.2, Vb7 or Vb2 (7,8,16). This population is able to recognize the glycolipid ligand a-galactosylceramide (aGalCer) bound to CD1d. Yet, existence of a smaller, so-called variant (or type II), CD1d-restriced NKT-cell population was also shown [8,9] This population expresses a diverse repertoire of TCRab and is unable to recognize aGalCer.Ã These authors contributed equally to this work. 3125The biological function of NKT cells seems paradoxical. They are able to rapidly produce large amounts of either T H 1 or T H 2 as well as T H 17 cytokines [10,11] and might promote immune responses in some settings but suppress cell-mediated immun...

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confidence: 93%

ICOS‐dependent stimulation of NKT cells by marginal zone B cells

et al. 2011

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“…V␣14 ϩ NKT cells have been shown to "cross-talk" with other lymphocytes, including NK, B, and T cells (15,16). In particular, it has been shown that NKT-NK cell interactions may play an important role in tumor surveillance in vivo (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

“…V␣14 ϩ NKT cells recognize an endogenous lysosomal glycosphingolipid, isoglobotrihexosylceramide (12), and when activated through their TCR or by soluble factors (such as IL-12) can produce both IFN-␥ and IL-4 (13,14). Moreover, V␣14 ϩ NKT cells have been shown to transactivate B, T, and NK cells in vivo (15,16). Along these lines, V␣14 ϩ NKT cells may act as sentinels to integrate initial signals following immune stimulation and thereby serve to orient subsequent immune responses.…”

Section: Invariant V␣14 ؉ Nkt Cells Participate In the Early Responsementioning

confidence: 99%

“…Since V␣14 ϩ NKT cells have been demonstrated to transactivate ␥␦ T cells, NK cells, and CD8 ␣␤ T cells after TCR stimulation (15,16), we asked whether this transactivation also occurred after infection by L. monocytogenes. We therefore analyzed the kinetics of NK cell IFN-␥ production in L. monocytogenes-infected C57BL/6 mice compared with V␣14 ϩ NKT cell-deficient J␣18°m ice ( Fig.…”

Section: V␣14 ϩ Nkt Cells Transctivate Nk Cells For Ifn-␥ Production mentioning

confidence: 99%

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Invariant Vα14+ NKT Cells Participate in the Early Response to EntericListeria monocytogenesInfection

Ranson

Bregenholt

Lehuen

et al. 2005

The Journal of Immunology

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Invariant Vα14+ NKT cells are a specialized CD1-reactive T cell subset implicated in innate and adaptive immunity. We assessed whether Vα14+ NKT cells participated in the immune response against enteric Listeria monocytogenes infection in vivo. Using CD1d tetramers loaded with the synthetic lipid α-galactosylceramide (CD1d/αGC), we found that splenic and hepatic Vα14+ NKT cells in C57BL/6 mice were early producers of IFN-γ (but not IL-4) after L. monocytogenes infection. Adoptive transfer of Vα14+ NKT cells derived from TCRα° Vα14-Jα18 transgenic (TCRα°Vα14Tg) mice into alymphoid Rag°γc° mice demonstrated that Vα14+ NKT cells were capable of providing early protection against enteric L. monocytogenes infection with systemic production of IFN-γ and reduction of the bacterial burden in the liver and spleen. Rechallenge experiments demonstrated that previously immunized wild-type and Jα18° mice, but not TCRα° or TCRα°Vα14Tg mice, were able to mount adaptive responses to L. monocytogenes. These data demonstrate that Vα14+ NKT cells are able to participate in the early response against enteric L. monocytogenes through amplification of IFN-γ production, but are not essential for, nor capable of, mediating memory responses required to sterilize the host.

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“…Murine iNK T cell activation in vivo with ␣GalCer induces IL-4-dependent expression of activation markers CD69, B7-2, and I-A b on B cells (9), and human NK T cell activation in vitro with ␣GalCer induces IL-4/IL-13-dependent B cell proliferation and total IgM, IgG1 antibody production (10). Reduced antibody responses in CD1d Ϫ/Ϫ or J␣18 Ϫ/Ϫ mice compared with WT mice during infection or autoimmune disease (3)(4)(5)11) is also consistent with iNK T cells and B cell cooperation.…”

Section: Nnate-like Lymphocytes Natural Killer (Nk) T Cells ␥␦ T Cmentioning

confidence: 99%