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Distinct APCs Explain the Cytokine Bias of &agr;-Galactosylceramide Variants In Vivo.
- Source :
-
Journal of Immunology . 4/1/2012, Vol. 188 Issue 7, p3053-3061. 9p. - Publication Year :
- 2012
-
Abstract
- &agr;-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 cdldlfl/fl mice, we demonstrated that distinct APC types explained the cytokine bias in vivo. Whereas NKT stimulation by &agr;-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-&ggr;, 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 Thl or Th2 cellular networks by changing APC targeting in vivo. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 188
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 77344498
- Full Text :
- https://doi.org/10.4049/jimmunol.1102414