Attenuation of invariant natural killer T-cell anergy induction through intradermal delivery of alpha-galactosylceramide.
CD1d restricted, alpha-galactosylceramide (alphaGC) responsive invariant (i)NKT cells positively regulate immune responses. Both intravenous and intradermal administered alphaGC are known to activate iNKT cells. iNKT cells become unresponsive to a second intravenous alphaGC injection, whereas no data are available regarding potential anergy upon intradermal administration. Here, comparative analysis of two intradermal versus two intravenous injections in mice demonstrated that iNKT cell anergy was prevented by intradermal injection and when combined with a vaccine, superior tumor protection afforded by intradermally administered alphaGC. Moreover, human skin dendritic cells (DC) took up intradermally injected alphaGC and activated iNKT cells upon migration, while iNKT cells in human skin-draining lymph nodes expanded in response to alphaGC presented either by exogenously added DC or by CD1d positive antigen presenting cells in the lymph nodes. In conclusion, glycolipids such as alphaGC may greatly improve the efficacy of skin immunization strategies, targeting cutaneous and lymph node DC.
Bontkes
Hetty J
HJ
Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. hj.bontkes@vumc.nl
Moreno
María
M
Hangalapura
Basav
B
Lindenberg
Jelle J
JJ
de Groot
Jan
J
Lougheed
Sinéad
S
van der Vliet
Hans J J
HJ
van den Eertwegh
Alfons J M
AJ
de Gruijl
Tanja D
TD
von Blomberg
B Mary E
BM
Scheper
Rik J
RJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D017951:Antigen Presentation; D049109:Cell Proliferation; D017635:Clonal Anergy; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage* / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed; D007114:Immunization / Q000379:methods; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D010047:Ovalbumin