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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2003-10, Vol.171 (8), p.4020-4027
Main Authors: Crowe, Nadine Y, Uldrich, Adam P, Kyparissoudis, Konstantinos, Hammond, Kirsten J. L, Hayakawa, Yoshihiro, Sidobre, Stephane, Keating, Rachael, Kronenberg, Mitchell, Smyth, Mark J, Godfrey, Dale I
Format: Article
Language:English
Subjects:
Animals
Antigens - administration & dosage
Antigens - pharmacology
Cell Division - immunology
Cell Separation
Cell Survival - immunology
Down-Regulation - immunology
Galactosylceramides - administration & dosage
Galactosylceramides - immunology
Galactosylceramides - pharmacology
Injections, Intraperitoneal
Interferon-gamma - biosynthesis
Interleukin-4 - biosynthesis
Killer Cells, Natural - cytology
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Liver - cytology
Liver - immunology
Lymphocyte Activation - immunology
Mice
Mice, Inbred C57BL
Organ Specificity - immunology
Receptors, Immunologic - antagonists & inhibitors
Receptors, Immunologic - biosynthesis
T-Lymphocyte Subsets - cytology
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Time Factors
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.171.8.4020