Critical Role for CD1d-restricted Invariant NKT Cells in Stimulating Intrahepatic CD8 T-cell Responses to Liver Antigen

Overview

Journal Gastroenterology

Specialty Gastroenterology

Date 2008 Jun 14

PMID 18549881

Citations 16

Authors

Dave Sprengers

Fenna C M Sille

Katja Derkow

Gurdyal S Besra

Harry L A Janssen

Eckart Schott

Marianne Boes

Affiliations

Soon will be listed here.

Abstract

Background & Aims: V alpha14 invariant natural killer T cells (iNKT) are localized in peripheral tissues such as the liver rather than lymphoid tissues. Therefore, their role in modulating the stimulation of conventional, major histocompatibility complex (MHC)-restricted T-cell responses has remained ambiguous. We here describe a role for V alpha14 iNKT cells in modulating conventional T-cell responses to antigen expressed in liver, using transferrin-mOVA (Tf-mOVA) mice.

Methods: Naïve ovalbumin-specific class I MHC-restricted T cells (OTI) were adoptively transferred into Tf-mOVA mice in the presence or absence of iNKT-cell agonist alpha-galactosylceramide, after which OTI T-cell priming, antigen-specific cytokine production, cytotoxic killing ability, and liver damage were analyzed.

Results: Transfer of OTI cells resulted in robust intrahepatic, antigen-specific proliferation of T cells. OTI T cells were activated in liver, and antigen-specific effector function was stimulated by coactivation of Valpha14 iNKT cells using alpha-galactosylceramide. This stimulation was absent in CD1d(-/-)Tf-mOVA mice, which lack V alpha14 iNKT cells, and was prevented when interferon-gamma and tumor necrosis factor-alpha production by V alpha14 iNKT cells was blocked.

Conclusions: CD1d-restricted V alpha14 iNKT cells stimulate intrahepatic CD8 T-cell effector responses to antigen expressed in liver. Our findings elucidate a previously unknown intervention point for targeted immunotherapy to autoimmune and possibly infectious liver diseases.

Citing Articles

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Zimmerer J, Ringwald B, Chaudhari S, Han J, Peterson C, Warren R J Immunol. 2021; 207(12):3107-3121.

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Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses.

Dolen Y, Valente M, Tagit O, Jager E, van Dinther E, van Riessen N Oncoimmunology. 2021; 9(1):1738813.

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Inflammatory Phenotype of Intrahepatic Sulfatide-Reactive Type II NKT Cells in Humans With Autoimmune Hepatitis.

Sebode M, Wigger J, Filpe P, Fischer L, Weidemann S, Krech T Front Immunol. 2019; 10:1065.

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The Role of CD1d and MR1 Restricted T Cells in the Liver.

Huang W, He W, Shi X, He X, Dou L, Gao Y Front Immunol. 2018; 9:2424.

PMID: 30425710 PMC: 6218621. DOI: 10.3389/fimmu.2018.02424.

The Role of Invariant NKT in Autoimmune Liver Disease: Can Vitamin D Act as an Immunomodulator?.

Smyk D, Mavropoulos A, Mieli-Vergani G, Vergani D, Lenzi M, Bogdanos D Can J Gastroenterol Hepatol. 2018; 2018:8197937.

PMID: 30046564 PMC: 6038587. DOI: 10.1155/2018/8197937.

References

Biburger M, Tiegs G . Alpha-galactosylceramide-induced liver injury in mice is mediated by TNF-alpha but independent of Kupffer cells. J Immunol. 2005; 175(3):1540-50. DOI: 10.4049/jimmunol.175.3.1540. View

Lanzavecchia A, Sallusto F . Regulation of T cell immunity by dendritic cells. Cell. 2001; 106(3):263-6. DOI: 10.1016/s0092-8674(01)00455-x. View

Hogquist K, Jameson S, Heath W, Howard J, Bevan M, Carbone F . T cell receptor antagonist peptides induce positive selection. Cell. 1994; 76(1):17-27. DOI: 10.1016/0092-8674(94)90169-4. View

Hermans I, Silk J, Gileadi U, Salio M, Mathew B, Ritter G . NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol. 2003; 171(10):5140-7. DOI: 10.4049/jimmunol.171.10.5140. View

Fujii S, Shimizu K, Smith C, Bonifaz L, Steinman R . Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein. J Exp Med. 2003; 198(2):267-79. PMC: 2194082. DOI: 10.1084/jem.20030324. View

Gallatin W, Weissman I, Butcher E . A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature. 1983; 304(5921):30-4. DOI: 10.1038/304030a0. View

Exley M, Bigley N, Cheng O, Tahir S, Smiley S, Carter Q . CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus. J Leukoc Biol. 2001; 69(5):713-8. View

Kita H, Naidenko O, Kronenberg M, Ansari A, Rogers P, He X . Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer. Gastroenterology. 2002; 123(4):1031-43. DOI: 10.1053/gast.2002.36020. View

Osman Y, Kawamura T, Naito T, Takeda K, Van Kaer L, Okumura K . Activation of hepatic NKT cells and subsequent liver injury following administration of alpha-galactosylceramide. Eur J Immunol. 2000; 30(7):1919-28. DOI: 10.1002/1521-4141(200007)30:7<1919::AID-IMMU1919>3.0.CO;2-3. View

10.

Matsuda J, Naidenko O, Gapin L, Nakayama T, Taniguchi M, Wang C . Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J Exp Med. 2000; 192(5):741-54. PMC: 2193268. DOI: 10.1084/jem.192.5.741. View

11.

Klein I, Gassel H, Crispe I . Cytotoxic T-cell response following mouse liver transplantation is independent of the initial site of T-cell priming. Transplant Proc. 2006; 38(10):3241-3. DOI: 10.1016/j.transproceed.2006.10.157. View

12.

Brossay L, Burdin N, Tangri S, Kronenberg M . Antigen-presenting function of mouse CD1: one molecule with two different kinds of antigenic ligands. Immunol Rev. 1998; 163:139-50. DOI: 10.1111/j.1600-065x.1998.tb01193.x. View

13.

Fujii H, Seki S, Kobayashi S, Kitada T, Kawakita N, Adachi K . A murine model of NKT cell-mediated liver injury induced by alpha-galactosylceramide/d-galactosamine. Virchows Arch. 2005; 446(6):663-73. DOI: 10.1007/s00428-005-1265-8. View

14.

Bowen D, Zen M, Holz L, Davis T, McCaughan G, Bertolino P . The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity. J Clin Invest. 2004; 114(5):701-12. PMC: 514586. DOI: 10.1172/JCI21593. View

15.

Inui T, Nakashima H, Habu Y, Nakagawa R, Fukasawa M, Kinoshita M . Neutralization of tumor necrosis factor abrogates hepatic failure induced by alpha-galactosylceramide without attenuating its antitumor effect in aged mice. J Hepatol. 2005; 43(4):670-8. DOI: 10.1016/j.jhep.2005.02.027. View

16.

Wuensch S, Pierce R, Crispe I . Local intrahepatic CD8+ T cell activation by a non-self-antigen results in full functional differentiation. J Immunol. 2006; 177(3):1689-97. DOI: 10.4049/jimmunol.177.3.1689. View

17.

Derkow K, Loddenkemper C, Mintern J, Kruse N, Klugewitz K, Berg T . Differential priming of CD8 and CD4 T-cells in animal models of autoimmune hepatitis and cholangitis. Hepatology. 2007; 46(4):1155-65. DOI: 10.1002/hep.21796. View

18.

Winau F, Hegasy G, Weiskirchen R, Weber S, Cassan C, Sieling P . Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity. 2007; 26(1):117-29. DOI: 10.1016/j.immuni.2006.11.011. View

19.

Van Kaer L . alpha-Galactosylceramide therapy for autoimmune diseases: prospects and obstacles. Nat Rev Immunol. 2005; 5(1):31-42. DOI: 10.1038/nri1531. View

20.

Lucas M, Gadola S, Meier U, Young N, Harcourt G, Karadimitris A . Frequency and phenotype of circulating Valpha24/Vbeta11 double-positive natural killer T cells during hepatitis C virus infection. J Virol. 2003; 77(3):2251-7. PMC: 140901. DOI: 10.1128/jvi.77.3.2251-2257.2003. View