Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency

Gerhard Wingender, Philippe Krebs, Bruce Beutler, Mitchell Kronenberg

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Invariant NKT (iNKT) cells are a unique subset of T lymphocytes that rapidly carry out effector functions following activation with glycolipid Ags, such as the model Ag α-galactosylceramide. Numerous studies have investigated the mechanisms leading to Th1 and Th2 cytokine production by iNKT cells, as well as the effects of the copious amounts of cytokines these cells produce. Less is known, however, about the mechanisms of iNKT cell cytotoxicity. In this study, we investigated the effect of Ag availability and strength, as well as the molecules involved in iNKT cytotoxicity. We demonstrate that the iNKT cell cytotoxicity in vivo correlates directly with the amount of CD1d expressed by the targets as well as the TCR affinity for the target glycolipid Ag. iNKT cells from spleen, liver, and thymus were comparable in their cytotoxicity in vitro. Surprisingly, we show that the Ag-specific cytotoxicity of iNKT cells in vivo depended almost exclusively on the interaction of CD95 (Fas) with CD178 (FasL), and that this mechanism can be efficiently used for tumor protection. Therefore, unlike NK cells, which rely mostly on perforin/granzyme-mediated mechanisms, the Ag-specific cytotoxicity of iNKT cells in vivo is largely restricted to the CD95/CD178 pathway.

Original languageEnglish (US)
Pages (from-to)2721-2729
Number of pages9
JournalJournal of Immunology
Volume185
Issue number5
DOIs
StatePublished - Sep 1 2010

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Natural Killer T-Cells
Antigens
Glycolipids
Galactosylceramides
Cytokines
Granzymes
Perforin
T-Lymphocyte Subsets
Natural Killer Cells
Thymus Gland
Spleen
Liver

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency. / Wingender, Gerhard; Krebs, Philippe; Beutler, Bruce; Kronenberg, Mitchell.

In: Journal of Immunology, Vol. 185, No. 5, 01.09.2010, p. 2721-2729.

Research output: Contribution to journalArticle

Wingender, Gerhard ; Krebs, Philippe ; Beutler, Bruce ; Kronenberg, Mitchell. / Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency. In: Journal of Immunology. 2010 ; Vol. 185, No. 5. pp. 2721-2729.
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