Journal
JOURNAL OF IMMUNOLOGY
Volume 188, Issue 7, Pages 3053-3061Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1102414
Keywords
-
Categories
Funding
- Major State Basic Research Development Program of China (973 program) [2012CB825806]
- National Natural Sciences Foundation of China [31021061]
- National Institutes of Health [AI038339, AI053725]
- Digestive Disease Research Core Center [P30 DK42086]
Ask authors/readers for more resources
alpha-Galactosylceramide represents a new class of vaccine adjuvants and immunomodulators that stimulate NKT cells to secrete Th1 and Th2 cytokines. Synthetic variants with short or unsaturated acyl chains exhibit a striking Th2 bias in vivo but no evidence of defect in TCR signaling or stimulation of NKT cells in vitro. Using cd1d1(fl/fl) mice, we demonstrated that distinct APC types explained the cytokine bias in vivo. Whereas NKT stimulation by a-Galactosylceramide required CD1d expression by dendritic cells (DCs), presentation of the Th2 variants was promiscuous and unaffected by DC-specific ablation of CD1d. This DC-independent stimulation failed to activate the feedback loop between DC IL-12 and NK cell IFN-gamma, explaining the Th2 bias. Conversely, forced presentation of the Th2 variants by DC induced high IL-12. Thus, lipid structural variations that do not alter TCR recognition can activate distinct Th1 or Th2 cellular networks by changing APC targeting in vivo. The Journal of Immunology, 2012, 188: 3053-3061.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available