The immunoregulatory role of CD1d-restricted natural killer T cells in disease

Vliet, Hans J. van der; Molling, Johan W.; Blomberg, B. Mary E. von; Nishi, Nobusuke; Kölgen, Wendy; Eertwegh, Alfons J.M. van den; Pinedo, H.M.; Giaccone, Giuseppe; Scheper, Rik J.

doi:10.1016/j.clim.2004.03.003

Cited by 108 publications

(100 citation statements)

References 173 publications

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“…However, clinical application of α-GalCer should be employed with caution since there are several concerns that may limit translation of the preclinical studies. It is still not clear how α-GalCer-mediated NKT cell stimulation can suppress Th1 mediated autoimmune diseases and also prevent tumor metastases and infections [113]. Moreover, in many of the studies of autoimmune diseases in mice, timing and dosage of α-GalCer had a significant impact on the disease outcome [93].…”

Section: Therapeutic Application Of α-Galcer Based Therapies For Automentioning

confidence: 99%

Immunoregulation of Autoimmunity by Natural Killer T Cells

2005

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Section: Therapeutic Application Of α-Galcer Based Therapies For Automentioning

confidence: 99%

Immunoregulation of Autoimmunity by Natural Killer T Cells

2005

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“…The glycolipid antigen α-Galactosylceramide (α-GalCer) presented by CD1d molecule could stimulate iNKT cells to rapidly produce abundant T-helper 1 (Th1) (e.g., IFN-γ) and T-helper 2 (Th2) cytokines (e.g., IL-4, IL-10) along with chemokines (5-9). As for tumor immunity, Th1 cytokines are associated with protective responses whereas Th2 cytokines are associated with suppression of tumor immunity (10). Thus, it was not surprising that the phase I clinical trial of α-GalCer showed meager antitumor responses, perhaps as a consequence of counteraction of Th1 cytokines by the Th2 cytokines (11)(12)(13).…”

mentioning

confidence: 99%

Avidity of CD1d-ligand-receptor ternary complex contributes to T-helper 1 (Th1) polarization and anticancer efficacy

Lin

Chang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Invariant natural killer T cell (NKT) cells (iNKT cells) produce both T-helper 1 (Th1) and T-helper 2 cytokines in response to α-Galactosylceramide (α-GalCer) stimulation and are thought to be the important effectors in the regulation of both innate and adaptive immunity involved in autoimmune disorders, microbial infections, and cancers. However, the anticancer effects of α-GalCer were limited in early clinical trial. In this study, several analogs of α-GalCer, containing phenyl groups in the lipid tails were found to stimulate murine and human iNKT cells to secrete Th1-skewed cytokines and exhibit greater anticancer efficacy in mice than α-GalCer. We explored the possibility of different Vβ usages of murine Vα14 iNKT or human Vα24 iNKT cells, accounting for differential cytokine responses. However, T-cell receptor Vβ analysis revealed no significant differences in Vβ usages by α-GalCer and these phenyl glycolipid analogs. On the other hand, these phenyl glycolipids showed greater binding avidity and stability for iNKT T-cell receptor when complexed with CD1d. These findings suggest that CD1d-phenyl glycolipid complexes may interact with the same population of iNKT cells but with higher avidity and stability to drive Th1 polarization. Thus, this study provides a key to the rational design of Th1 biased CD1d reactive glycolipids in the future.immune-modulating activity | structure | interaction | cancer immunotherapy

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“…The iNKT cells participate in immunoregulation through their ability to rapidly produce large amounts of regulatory cytokines such as IFN-␥ and IL-4, and also by influencing the recruitment and differentiation of dendritic cells (DCs) (2)(3)(4). Their immunoregulatory functions have been emphasized in studies of multiple autoimmune diseases, in which defects of iNKT cell numbers or functions are associated with disease progression (5). In addition, there is abundant evidence implicating iNKT cells in protective immunity against microbial pathogens, and also in host responses to malignancies (6).…”

mentioning

confidence: 99%

Expression of CD1d Molecules by Human Schwann Cells and Potential Interactions with Immunoregulatory Invariant NK T Cells

Im¹,

Tapinos

Chae³

et al. 2006

The Journal of Immunology

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CD1d-restricted NKT cells expressing invariant TCR α-chains (iNKT cells) produce both proinflammatory and anti-inflammatory cytokines rapidly upon activation, and are believed to play an important role in both host defense and immunoregulation. To address the potential implications of iNKT cell responses for infectious or inflammatory diseases of the nervous system, we investigated the expression of CD1d in human peripheral nerve. We found that CD1d was expressed on the surface of Schwann cells in situ and on primary or immortalized Schwann cell lines in culture. Schwann cells activated iNKT cells in a CD1d-dependent manner in the presence of α-galactosylceramide. Surprisingly, the cytokine production of iNKT cells stimulated by α-galactosylceramide presented by CD1d+ Schwann cells showed a predominance of Th2-associated cytokines such as IL-5 and IL-13 with a marked deficiency of proinflammatory Th1 cytokines such as IFN-γ or TNF-α. Our findings suggest a mechanism by which iNKT cells may restrain inflammatory responses in peripheral nerves, and raise the possibility that the expression of CD1d by Schwann cells could be relevant in the pathogenesis of infectious and inflammatory diseases of the peripheral nervous system.

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The immunoregulatory role of CD1d-restricted natural killer T cells in disease

Cited by 108 publications

References 173 publications

Immunoregulation of Autoimmunity by Natural Killer T Cells

Immunoregulation of Autoimmunity by Natural Killer T Cells

Avidity of CD1d-ligand-receptor ternary complex contributes to T-helper 1 (Th1) polarization and anticancer efficacy

Expression of CD1d Molecules by Human Schwann Cells and Potential Interactions with Immunoregulatory Invariant NK T Cells

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