Retrovirally induced switch from production of IL-12 to IL-4 in dendritic cells

Eur J Immunol. 1999 Jul;29(7):2309-18. doi: 10.1002/(SICI)1521-4141(199907)29:07<2309::AID-IMMU2309>3.0.CO;2-5.


Dendritic cells (DC) in HIV-1 infection show a reduced capacity to stimulate primary T cell proliferation. Exposure of bone marrow-derived DC to Rauscher leukemia virus (RLV) provides a mouse model for studying retrovirally induced reduction in stimulatory capacity for T cells. Treatment with IL-12, a cytokine that promotes the development of Th1 cells, has been postulated as a treatment for AIDS and is effective at restoring cell-mediated immunity in mice infected with mouse AIDS virus or with RLV (see Knight, S. C. and Patterson, S., Annu. Rev. Immunol. 1994. 15: 593-615 for references). Here we studied the direct effect of RLV and of IL-12 on bone marrow-derived DC. Normal DC produced IL-12 and IL-10 and stimulated primary allogeneic T cell proliferation. Exposure of DC to RLV caused reduced production of IL-12, production of IL-4 was seen in DC for the first time and T cell stimulation was inhibited. Addition of IL-12 reinstated and enhanced IL-12 synthesis in RLV-treated DC, abrogated production of IL-10 and IL-4 and restored stimulatory activity. Manipulation of cytokine production in DC could be a stratagem that has evolved in the retrovirus to avoid stimulation of cellular responses.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • Dendritic Cells / immunology*
  • HIV Infections / immunology
  • HIV-1
  • Humans
  • Immune Tolerance
  • In Vitro Techniques
  • Interleukin-12 / biosynthesis*
  • Interleukin-4 / biosynthesis*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Rauscher Virus / genetics
  • Rauscher Virus / immunology*
  • Rauscher Virus / pathogenicity
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • DNA Primers
  • DNA, Viral
  • Interleukin-12
  • Interleukin-4