Glycolipid antigen drives rapid expansion and sustained cytokine production by NK T cells.
NKT cells are enigmatic lymphocytes that respond to glycolipid Ags presented by CD1d. Although they are key immunoregulatory cells, with a critical role in immunity to cancer, infection, and autoimmune diseases, little is known about how they respond to antigenic challenge. Current theories suggest that NKT cells die within hours of stimulation, implying that their direct impact on the immune system derives from the initial cytokine burst released before their death. Here we show that NKT cell disappearance results from TCR down-regulation rather than apoptosis, and that they expand to many times their normal number in peripheral tissues within 2-3 days of stimulation, before contracting to normal numbers over subsequent days. This expansion is associated with ongoing cytokine production, biased toward a Th1 (IFN-gamma(+) IL-4(-)) phenotype, in contrast to their initial Th0 (IFN-gamma(+)IL-4(+)) phenotype. This study provides critical new insight into how NKT cells can have such a major impact on immune responses, lasting many days beyond the initial stimulation of these cells.
Crowe
Nadine Y
NY
Department of Pathology and Immunology, Monash University, Central and Eastern Clinical School, Prahran, Victoria, Australia.
Uldrich
Adam P
AP
Kyparissoudis
Konstantinos
K
Hammond
Kirsten J L
KJ
Hayakawa
Yoshihiro
Y
Sidobre
Stephané
S
Keating
Rachael
R
Kronenberg
Mitchell
M
Smyth
Mark J
MJ
Godfrey
Dale I
DI
D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000494:pharmacology; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005699:Galactosylceramides / Q000008:administration & dosage* / Q000276:immunology* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000276:immunology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000941:Antigens; D005699:Galactosylceramides; D011971:Receptors, Immunologic; D015847:Interleukin-4; D007371:Interferon-gamma