Differential Regulation of Th1 and Th2 Functions of NKT Cells by CD28 and CD40 Costimulatory Pathways

Hayakawa, Yoshihiro; Takeda, Kazuyoshi; Yagita, Hideo; Kaer, Luc Van; Saiki, Ikuo; Okumura, Ko

doi:10.4049/jimmunol.166.10.6012

Cited by 183 publications

(192 citation statements)

References 55 publications

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“…In fact, the down-modulation of CD40L upon SEB priming could reflect 'type-2' NK T cells. It was demonstrated, previously, that the ligation of CD40L is of fundamental importance for NK T cells to secrete IFN-c. 50 Our results would be consistent with the possibility that the downmodulation of CD40L on NK T cells by SEB activation would result in a Th2 functional pattern by the lack of CD40L coaggregation upon re-stimulation. In addition to CD40L molecules, ICOS was also described as crucial for the development and maintenance of humoral immune responses.…”

Section: Discussionsupporting

confidence: 80%

Natural killer T cells are required for the development of a superantigen‐driven T helper type 2 immune response in mice

et al. 2005

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SummaryWe show, here, that one single injection or weekly injections of staphylococcal enterotoxin B (SEB), starting in 1-day-old newborn mice, induced a powerful immune response with a T helper type 2 (Th2) pattern, as judged by the isotype and cytokine profile, with the production of large amounts of SEB-specific immunoglobulin G1 (IgG1), detectable levels of SEB-specific IgE and increased production of interleukin-4 by spleen cells. These protocols also induced an increase in the levels of total IgE in the serum. Memory of SEB was transferred to secondary recipients by using total spleen cells from primed animals. The secondary humoral response in transferred mice was diminished if spleen cells from SEB-treated mice were previously depleted of CD3 + or Vb8 + T cells or NK1.1 + cells. In vivo depletion of NK1.1 + cells in adult mice resulted in a marked reduction in the SEB-specific antibody response in both the primary and secondary immune responses. Additionally, purified NK1.1 + T cells were able to perform SEB-specific helper B-cell actions in vitro and in vivo. These results suggest that NK1.1 + T cells are required for the full development of humoral immunological memory, whilst making neonatal tolerance to SEB unachievable.

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Section: Discussionsupporting

confidence: 80%

Natural killer T cells are required for the development of a superantigen‐driven T helper type 2 immune response in mice

et al. 2005

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“…3b). Thus, costimulatory signals from CD28 and CD40 were not sufficient for the potentiation of iNKT cells, although they might modulate the cytokine profile of the activated iNKT cells, as previously reported (8).…”

Section: Cd1d Expression Of Dcs But Not Costimulatory Molecules and supporting

confidence: 59%

Efficient Activation of Vα14 Invariant NKT Cells by Foreign Lipid Antigen Is Associated with Concurrent Dendritic Cell-Specific Self Recognition

Ueno

Cho

et al. 2007

The Journal of Immunology

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A burst release of cytokines by Vα14 invariant NKT (iNKT) cells upon their TCR engagement critically regulates innate and adaptive immune responses. However, it remains unclear in vivo why iNKT cells respond efficiently to microbial or intracellular lipid Ags that are at low levels or that possess suboptimal antigenicity. We found that dendritic cells (DCs) potentiated iNKT cells to respond to a minimal amount of ligand α-galactosylceramide (αGalCer) through CD1d-dependent autoreactive responses that require endosomal processing and CD1d trafficking. The ability of potentiation of NKT cells was DC specific and did not depend on costimulatory signals and IL-12 production by DCs. However, DCs that failed to synthesize a major endogenous lipid Ag isoglobotrihexosylceramide were unable to potentiate NKT cells for efficient activation. Further analysis showed that differences in the level and pattern of endogenous lipid Ag presentation differentiate DCs and B cells for effective potentiation and subsequent activation of iNKT cells in the presence of an exogenous Ag. Thus, CD1d-dependent potentiation by DCs may be crucial for iNKT cell-mediated immunity against infectious agents.

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“…The particular costimulatory molecules that could account for this difference and might be lacking from Schwann cells have not yet been determined. However, studies of murine iNKT cells have established that costimulation through CD28 and ICOS are required for maximal responses of these cells, suggesting that the ligands for these costimulatory receptors may be lacking on the Schwann cells that we have studied (44,45).…”

Section: Discussionmentioning

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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Differential Regulation of Th1 and Th2 Functions of NKT Cells by CD28 and CD40 Costimulatory Pathways

Cited by 183 publications

References 55 publications

Natural killer T cells are required for the development of a superantigen‐driven T helper type 2 immune response in mice

Natural killer T cells are required for the development of a superantigen‐driven T helper type 2 immune response in mice

Efficient Activation of Vα14 Invariant NKT Cells by Foreign Lipid Antigen Is Associated with Concurrent Dendritic Cell-Specific Self Recognition

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

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