Retrovirally induced switch from production of IL-12 to IL-4 in dendritic cells.
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.
Kelleher
P
P
Antigen Presentation Research Group, Imperial College School of Medicine, Northwick Park Institute for Medical Research, Harrow, Middlesex, GB.
Maroof
A
A
Knight
S C
SC
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D003713:Dendritic Cells / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011925:Rauscher Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D017931:DNA Primers; D004279:DNA, Viral; D018664:Interleukin-12; D015847:Interleukin-4