Selective Conditions Are Required for the Induction of Invariant NKT Cell Hyporesponsiveness by Antigenic Stimulation.
Activation of invariant (i)NKT cells with the model Ag α-galactosylceramide induces rapid production of multiple cytokines, impacting a wide variety of different immune reactions. In contrast, following secondary activation with α-galactosylceramide, the behavior of iNKT cells is altered for months, with the production of most cytokines being strongly reduced. The requirements for the induction of this hyporesponsive state, however, remain poorly defined. In this study, we show that Th1-biasing iNKT cell Ags could induce iNKT cell hyporesponsiveness, as long as a minimum antigenic affinity was reached. In contrast, the Th2-biasing Ag OCH did not induce a hyporesponsive state, nor did cytokine-driven iNKT cell activation by LPS or infections. Furthermore, although dendritic cells and B cells have been reported to be essential for iNKT cell stimulation, neither dendritic cells nor B cells were required to induce iNKT cell hyporesponsiveness. Therefore, our data indicate that whereas some bone marrow-derived cells could induce iNKT cell hyporesponsiveness, selective conditions, dependent on the structure and potency of the Ag, were required to induce hyporesponsiveness.
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, 35340 Balcova/Izmir, Turkey; gerhard.wingender@deu.edu.tr mitch@lji.org.
Gerhard
G
Wingender
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Alysia M
AM
Birkholz
Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, 35340 Balcova/Izmir, Turkey; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
Duygu
D
Sag
Department of Chemistry, University of Connecticut, Storrs, CT 06269.
Elisa
E
Farber
Department of Chemistry, University of Connecticut, Storrs, CT 06269.
Sampada
S
Chitale
Department of Chemistry, University of Connecticut, Storrs, CT 06269.
Amy R
AR
Howell
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Mitchell
M
Kronenberg
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide