Distinct APCs explain the cytokine bias of α-galactosylceramide variants in vivo.

نویسندگان

  • Li Bai
  • Michael G Constantinides
  • Seddon Y Thomas
  • Rachel Reboulet
  • Fanyong Meng
  • Frank Koentgen
  • Luc Teyton
  • Paul B Savage
  • Albert Bendelac
چکیده

α-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 α-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-γ, 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.

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عنوان ژورنال:
  • Journal of immunology

دوره 188 7  شماره 

صفحات  -

تاریخ انتشار 2012