NDLI: TCR-dependent and –independent activation underlie liver-specific regulation of NKT cells

Content Provider	PubMed Central
Author	Subleski, Jeff J. Hall, Veronica L. Wolfe, Thomas B. Scarzello, Anthony J. Weiss, Jonathan M. Chan, Tim Hodge, Deborah L. Back, Timothy C. Ortaldo, John R. Wiltrout, Robert H.
Abstract	The fate of iNKT cells following activation remains controversial and unclear. We systemically examined how iNKT cells are regulated following TCR-dependent and -independent activation with alpha-Galactosylceramide (αGC) or IL-18+IL-12 respectively. Our studies reveal activation by αGC or IL-18+IL-12 induced transient depletion of iNKT cells exclusively in the liver that was independent of caspase 3 mediated apoptosis. The loss of iNKT cells was followed by repopulation and expansion of phenotypically distinct cells via different mechanisms. Liver iNKT cell expansion following αGC, but not IL-18+IL-12, treatment required an intact spleen and IFN-γ. Additionally, IL-18+IL-12 induced a more prolonged expansion of liver iNKT cells compared to αGC. iNKT cells that repopulate the liver following αGC had higher levels of suppressive receptors PD-1 and Lag3 while those that repopulate the liver following IL-18+IL-12 had increased levels of TCR and ICOS. In contrast to acute treatment that caused a transient loss of iNKT cells, chronic αGC or IL-18+IL-12 treatment caused long-term systemic loss requiring an intact thymus for repopulation of the liver. This report reveals a previously undefined role for the liver in the depletion of activated iNKT cells. Additionally, TCR-dependent and -independent activation differentially regulate iNKT cell distribution and phenotype. These results provide new insights for understanding how iNKT cells are systemically regulated following activation.
Related Links	http://dx.doi.org/10.4049/jimmunol.1001735
Ending Page	847
Page Count	10
Starting Page	838
File Format	PDF
ISSN	15506606
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	2
Volume Number	186
Language	English
Publisher Date	2011-01-15
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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