Critical Proinflammatory and Anti-Inflammatory Functions of Different Subsets of CD1d-Restricted Natural Killer T Cells during<i>Trypanosoma cruzi</i>Infection

Duthie, Malcolm S.; Kahn, Maria; White, Maria P.; Kapur, Raj P.; Kahn, Stuart J.

doi:10.1128/iai.73.1.181-192.2005

Cited by 82 publications

(77 citation statements)

References 75 publications

(79 reference statements)

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“…Several studies on experimental models of autoimmune diseases, parasitic diseases, and antitumor immunity suggest that type I and type II NKT cells play opposite or cross-regulating roles (24,25,33,34). Thus, sulfatide-reactive type II NKT cells suppress antitumor immunity in several tumor models, whereas type I NKT cells promote immune responses against cancer (24,35).…”

Section: Discussionmentioning

confidence: 99%

Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a β-linked self-glycolipid

Arrenberg

Halder

Dai

et al. 2010

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

109

144

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TCR-mediated recognition of β-linked self-glycolipids bound to CD1d is poorly understood. Here, we have characterized the TCR repertoire of a CD1d-restricted type II NKT cell subset reactive to sulfatide involved in the regulation of autoimmunity and antitumor immunity. The sulfatide/CD1d-tetramer + cells isolated from naïve mice show an oligoclonal TCR repertoire with predominant usage of the Vα3/Vα1-Jα7/Jα9 and Vβ8.1/Vβ3.1-Jβ2.7 gene segments. The CDR3 regions of both the α- and β-chains are encoded by either germline or nongermline gene segments of limited lengths containing several conserved residues. Presence of dominant clonotypes with limited TCR gene usage for both TCR α- and β-chains in type II NKT cells reflects specific antigen recognition not found in the type I NKT cells but similar to the MHC-restricted T cells. Although potential CD1d-binding tyrosine residues in the CDR2β region are conserved between most type I and type II NKT TCRs, CDR 1α and 3α regions differ significantly between the two subsets. Collectively, the TCR repertoire of sulfatide-reactive type II NKT cells exhibits features of both antigen-specific conventional T cells and innate-like cells, and these findings provide important clues to the recognition of β-linked glycolipids by CD1d-restricted T cells in general.

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Section: Discussionmentioning

confidence: 99%

Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a β-linked self-glycolipid

Arrenberg

Halder

Dai

et al. 2010

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

109

144

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“…In murine Trypanasoma cruzi infection, CD1d KO mice were found to have a mild disease compared with J␣18 KO mice that had a much more severe inflammatory disease and died (116). This finding was interpreted to mean that type II NKT cells were proinflammatory in this disease whereas type I NKT cells might counteract the effect of type II when both were present.…”

Section: Type II Nkt Cells In Tumor Immunity and Immune Regulationmentioning

confidence: 99%

NKT Cells in Tumor Immunity: Opposing Subsets Define a New Immunoregulatory Axis

Berzofsky

Terabe

2008

The Journal of Immunology

109

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“…In some pathologic conditions, vNKT cells and iNKT cells exert opposing functions in immune regulation. 72,[75][76][77][78][79] To verify this, J␣18 Ϫ/Ϫ mice were reconstituted using pure iNKT cells. In this condition, although the kinetics of animal death was different than that of WT animals, 80% of mice died of infection.…”

Section: Discussionmentioning

confidence: 99%

“…80 Attempts are under way to investigate these issues and to identify other functions of iNKT cells in DENV-associated disease. In parallel, because iNKT cells and vNKT cells might have opposing roles during infection and inflammation, 72,[75][76][77][78][79] it would be interesting to examine the role of both subsets and their interplay during DENV infection.…”

Section: Discussionmentioning

confidence: 99%

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

Renneson¹,

Guabiraba²,

Maillet³

et al. 2011

The American Journal of Pathology

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Dengue virus (DENV), a member of the mosquitoborne flaviviruses, is a serious public health problem in many tropical countries. We assessed the in vivo physiologic contribution of invariant natural killer T (iNKT) cells, a population of nonconventional lipidreactive ␣␤ T lymphocytes, to the host response during experimental DENV infection. We used a mouseadapted DENV serotype 2 strain that causes a disease that resembles severe dengue in humans. On DENV challenge, splenic and hepatic iNKT cells became activated insofar as CD69 and Fas ligand up-regulation and interferon-␥ production. C57BL/6 mice deficient in iNKT cells (J␣18 ؊/؊ ) were more resistant to lethal infection than were wild-type animals, and the phe Dengue virus (DENV), a flavivirus of the Flaviviridae family, is a serious public health problem in tropical and subtropical areas. In the last 60 years, the incidence, distribution, and clinical severity of dengue-related diseases have increased dramatically. 1,2 There are an estimated 50 million to 100 million DENV infections each year, of which approximately 500,000 are severe dengue hemorrhagic fever, and 24,000 result in death. 2,3 DENV is a single-stranded RNA virus that is transmitted to humans by Aedes mosquitoes, primarily Aedes aegypti. Infection with any of the four serotypes of DENV results in clinical symptoms that range from classic dengue fever to severe dengue hemorrhagic fever and shock syndrome, as defined by the World Health Organization. 4 Severe forms are life-threatening and are characterized by hemorrhagic manifestations, hemoconcentration, thrombocytopenia, and increased vascular permeability. 1,5-10 Despite growing public health concerns, currently there is no vaccine and no specific theraSupported in part by the

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Critical Proinflammatory and Anti-Inflammatory Functions of Different Subsets of CD1d-Restricted Natural Killer T Cells duringTrypanosoma cruziInfection

Cited by 82 publications

References 75 publications

Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a β-linked self-glycolipid

Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a β-linked self-glycolipid

NKT Cells in Tumor Immunity: Opposing Subsets Define a New Immunoregulatory Axis

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

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