IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells

Leite‐de‐Moraes, Maria; Hameg, Agathe; Pacilio, Maria; Koezuka, Yasuhiko; Taniguchi, Masaru; Kaer, Luc Van; Schneider, Elke; Dy, Michel; Herbelin, André

doi:10.4049/jimmunol.166.2.945

Cited by 117 publications

(88 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One interpretation of these studies is that IL-18 is a potent inducer of IL-4 and IL-13 production by basophils and mast cells, or possibly CD4 + T cells. Indeed, induction of IL-4 production by IL-18 in NK T cells has recently been reported 35, which is consistent with our observation that unstimulated CD4 + NKT cells express high levels of IL-18Rα similar to NK cells (data not shown). Such a systemic production of IL-4 may facilitate the priming of antigen-specific CD4 + Th2 cells.…”

Section: Discussionsupporting

confidence: 93%

Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation

Smeltz

Chen

Hu‐Li

et al. 2001

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Interleukin (IL)-18 has been well characterized as a costimulatory factor for the induction of IL-12–mediated interferon (IFN)-γ production by T helper (Th)1 cells, but also can induce IL-4 production and thus facilitate the differentiation of Th2 cells. To determine the mechanisms by which IL-18 might regulate these diametrically distinct immune responses, we have analyzed the role of cytokines in the regulation of IL-18 receptor α chain (IL-18Rα) expression. The majority of peripheral CD4+ T cells constitutively expressed the IL-18Rα. Upon antigen stimulation in the presence of IL-12, marked enhancement of IL-18Rα expression was observed. IL-12–mediated upregulation of IL-18Rα required IFN-γ. Activated CD4+ T cells that expressed low levels of IL-18Rα could produce IFN-γ when stimulated with the combination of IL-12 and IL-18, while CD4+ cells which expressed high levels of IL-18Rα could respond to IL-18 alone. In contrast, T cell stimulation in the presence of IL-4 resulted in a downregulation of IL-18Rα expression. Both IL-4−/− and signal transducer and activator of transcription (Stat)6−/− T cells expressed higher levels of IL-18Rα after TCR stimulation. Furthermore, activated T cells from Stat6−/− mice produced more IFN-γ in response to IL-18 than wild-type controls. Thus, positive/negative regulation of the IL-18Rα by the major inductive cytokines (IL-12 and IL-4) determines the capacity of IL-18 to polarize an immune response.

show abstract

Section: Discussionsupporting

confidence: 93%

Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation

Smeltz

Chen

Hu‐Li

et al. 2001

The Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…It is interesting to consider our results in light of the observations that V␣14 ϩ NKT cells can produce both IFN-␥ and IL-4 following TCR stimulation in vitro. In contrast, V␣14 ϩ NKT cells can preferentially produce either IL-4 or IFN-␥ following stimulation with cytokines (37). The restricted biological activity of NKT cells after L. monocytogenes infection could indicate that these cells do not receive TCR stimulation via CD1d complexes in vivo in the setting.…”

Section: Discussionmentioning

confidence: 98%

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

Ranson

Bregenholt

Lehuen

et al. 2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…However, we have demonstrated that IL-18, in combination with IL-2 but not with IL-12, can be a strong cofactor for the expression of a Th2 cytokine, IL-13, in T cells and in a unique NK population (9,10). More recently, we and other groups have reported that IL-18 can potentially induce Th2 cytokines (IL-4, IL-5, IL-10, IL-13) and IgE and IgG1 production (11)(12)(13)(14)(15)(16), suggesting that IL-18 can act as a cofactor for both Th1 and Th2 cell development.…”

Section: Cutting Edge: Il-18-transgenic Mice: In Vivo Evidence Of a Bmentioning

confidence: 99%

Cutting Edge: IL-18-Transgenic Mice: In Vivo Evidence of a Broad Role for IL-18 in Modulating Immune Function

Hoshino

Kawase

Okamoto

et al. 2001

The Journal of Immunology

124

View full text Add to dashboard Cite

IL-18 has been shown to be a strong cofactor for Th1 T cell development. However, we previously demonstrated that when IL-18 was combined with IL-2, there was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells. More recently, we and other groups have reported that IL-18 can potentially induce IgE, IgG1, and Th2 cytokine production in murine experimental models. Here, we report on the generation of IL-18-transgenic (Tg) mice in which mature mouse IL-18 cDNA was expressed. CD8+CD44high T cells and macrophages were increased, but B cells were decreased in these mice while serum IgE, IgG1, IL-4, and IFN-γ levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-γ, IL-4, IL-5, and IL-13 than control wild-type mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.

show abstract

IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells

Cited by 117 publications

References 45 publications

Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation

Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation

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

Cutting Edge: IL-18-Transgenic Mice: In Vivo Evidence of a Broad Role for IL-18 in Modulating Immune Function

Contact Info

Product

Resources

About