OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice

Zaini, Jamal; Andarini, Sita; Tahara, Masaki; Saijo, Yasuo; Ishii, Naoto; Kawakami, Kazuyoshi; Taniguchi, Masaru; Sugamura, Kazuo; Nukiwa, Toshihiro; Kikuchi, Toshiaki

doi:10.1172/jci32693

Cited by 90 publications

(75 citation statements)

References 66 publications

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“…Costimulatory signals through CD28, ICOS, and OX40 contribute to the cytokine production and cytotoxic activity of a-GalCer-activated iNKT cells [15][16][17][19][20][21][22]. In addition, our results indicate that the lack of GITR signals enhances not only the cytokine production but also the proliferation of iNKT cells upon a-GalCer stimulation both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 84%

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Co‐inhibitory roles for glucocorticoid‐induced TNF receptor in CD1d‐dependent natural killer T cells

Chen¹,

Ndhlovu²,

Takahashi³

et al. 2008

Eur J Immunol

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Invariant natural killer T (iNKT) cells are a special subset of ab T cells with invariant TCR, which recognize a-galactosylceramide (a-GalCer) presented by CD1d. In addition to signals through the invariant TCR upon stimulation with a-GalCer, costimulatory signals, such as signals through CD28 and OX40, are indispensable for full activation of iNKT cells. In this study, we investigated the functions of a well-known costimulatory molecule, glucocorticoid-induced TNF receptor (GITR), on Ag-induced iNKT cell activation. Unexpectedly, engagement of GITR by agonistic mAb DTA-1 suppressed proliferation and cytokine production of iNKT cells upon a-GalCer stimulation. In addition, GITR signals in iNKT cells during only the Ag-priming phase was sufficient to inhibit the iNKT cell activation. Consistent with these results, the GITR-deficient iNKT cells showed enhanced proliferation and increased cytokine production upon a-GalCer stimulation both in vitro and in vivo. Furthermore, the in vivo administration of a-GalCer suppressed tumor metastasis more efficiently in GITR-deficient mice than in wild-type mice. Collectively, GITR plays a coinhibitory role in Ag-induced iNKT cell activation.

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Section: Discussionmentioning

confidence: 84%

“…We have also reported that signals through OX40, a well-known T cell costimulatory molecule, are essential for optimal activation of iNKT cells [22]. Thus, most T cell costimulatory molecules appeared to positively regulate NKT cell function.…”

Section: Introductionmentioning

confidence: 85%

Co‐inhibitory roles for glucocorticoid‐induced TNF receptor in CD1d‐dependent natural killer T cells

Chen¹,

Ndhlovu²,

Takahashi³

et al. 2008

Eur J Immunol

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“…Effective co-stimulation via CD28 or 4-1BB on iNKT cells has been shown to be required for optimal iNKT cell production of both IL-4 and IFNγ [92]. On the other hand, CD154-CD40, OX40L-OX40 interactions or engagement of CxCR6 cells seem important only for IFNγ production [93][94][95]. APCs activated by TLR signaling or by LPS can induce IFNγ but not IL-4 production by iNKT cells.…”

Section: The Influence Of the Microenvironment On The Inkt Cell Responsementioning

confidence: 99%

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

352

399

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SummaryNatural Killer T cells are a distinct lymphocyte lineage that regulates a broad range of immune responses. NKT cells recognize glycolipids presented by the non-classical MHC molecule CD1d. Structural insight into the TCR/glycolipid/CD1d tri-complex has revealed an unusual and unexpected mode of recognition. Recent studies have also identified some of the signaling events during NKT cell development that give NKT cells their innate phenotype. Pathogen-derived glycolipid antigens continue to be found, and new mechanisms of NKT cell activation have been described. Finally, NKT cells have been shown to be remarkably versatile in function during various immune responses. Whether these extensive functional capacities can be attributed to a single population sensitive to environmental cues or if functionally distinct NKT cell subpopulations exist remains unresolved.

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“…4,9 Consequently, mice lacking OX40L expression on mature DCs are unable to mount a specific cellular antitumor response. 41 Conversely, transfection of murine DCs with mRNA encoding OX40L augmented the induction of an antitumor response. 15 On human MoDCs, a rather weak induction of OX40L expression has been described after In the present study, we identify PGE 2 as a key factor for the expression of OX40L and CD70 on the surface of mature MoDCs (Figure 2) and PBDCs ( Figure 3A).…”

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confidence: 99%

Prostaglandin E2 enhances T-cell proliferation by inducing the costimulatory molecules OX40L, CD70, and 4-1BBL on dendritic cells

Krause

Brückner

Uermösi

et al. 2009

Blood

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Dendritic cell (DC)-based immunotherapy of malignant diseases relies on 2 critical parameters: antigen transport from the periphery to draining lymph nodes and efficient priming of primary and stimulation of secondary immune responses. Prostaglandin E 2 (PGE 2 ) signaling has been shown to be pivotal for DC migration toward lymph node-derived chemokines in vitro and in vivo. Here, we demonstrate that PGE 2 induced the expression of the costimulatory molecules OX40L, CD70, and 4-1BBL on human DCs. Short triggering by PGE 2 early during DC maturation was sufficient to induce the costimulatory molecules. The expression of the costimulatory molecules was independent of the maturation stimulus but strictly dependent on PGE 2 on both monocytederived (Mo) DCs and peripheral blood myeloid (PB) DCs. PGE 2 -matured MoDCs showed enhanced costimulatory capacities resulting in augmented antigenspecific CD4 ؉ and CD8 ؉ T-cell prolifera- IntroductionDendritic cells (DCs) are key players in the defense against pathogens because of their unique capacity to induce primary and secondary T-cell responses. By presenting specific antigens on major histocompatibility complex and by expressing costimulatory molecules, DCs provide essential signals for optimal T-cell activation, prevention of tolerance, and development of T-cell immunity. The most important costimulatory receptor for early proliferation of naive T cells is CD28, which interacts with CD80 or CD86 on DCs. 1 However, CD28-CD80/86 costimulatory interactions cannot fully account for an efficient long-lasting T-cell response or the generation of memory T cells. 2 T-cell proliferation and survival at later phases and the development of memory T cells depend on additional costimulatory molecules belonging to the tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily and include OX40L/OX40, 4-1BBL/4-1BB, and CD70/CD27. 3 OX40 is induced on activated T cells and provides an essential signal for optimal CD4 ϩ T-cell function 4-7 as well as for the generation of memory T cells [8][9][10] by prolonging the survival of effector T cells. 9 Signaling through OX40 is controlled in vivo by the availability of its ligand OX40L. The expression of OX40L is tightly regulated and can be induced on antigen-presenting cells (APCs), such as DCs 11,12 and B cells 13 and microglia. 14 The lack of OX40L on APCs results in a marked reduction of cytokine production and proliferation of T-helper cells. 5,7 Murine DCs transfected with mRNA encoding OX40L induce enhanced antitumor activity in vivo, whereas transfection of OX40L mRNA in human monocyte-derived (Mo) DCs improves the induction of antigen-specific cytotoxic T lymphocytes (CTLs) in vitro. 15 CD27 is expressed on naive CD4 ϩ and CD8 ϩ T cells 16 and on primed B cells, 17 and triggering of CD27 by CD70 supports T-cell survival. Consequently, constant activation of CD27 by persistent transgenic expression of CD70 on mouse B cells leads to excessive T-cell proliferation. 18,19 CD70 expression is transiently induced on T cells, B cells, a...

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OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice

Cited by 90 publications

References 66 publications

Co‐inhibitory roles for glucocorticoid‐induced TNF receptor in CD1d‐dependent natural killer T cells

Co‐inhibitory roles for glucocorticoid‐induced TNF receptor in CD1d‐dependent natural killer T cells

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Prostaglandin E2 enhances T-cell proliferation by inducing the costimulatory molecules OX40L, CD70, and 4-1BBL on dendritic cells

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