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

Dendritic cells (DC) in HIV-I infection show a reduced capacity to stimulat e primary T cell proliferation. Exposure of bone marrow-derived DC to Rausc her leukemia Virus (RLV) provides a mouse model for studying retrovirally i nduced 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 immuni ty in mice infected with mouse AIDS virus or with RLV (see Knight, S. C. an d Patterson, S., Annu. Rev. Immunol. 1994. 15: 593-615 for references). Her e we studied the direct effect of RLV and of IL-12 on bone marrow-derived D C. Normal DC produced IL-12 and IL-10 and stimulated primary allogeneic T c ell 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 stimulati on 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 sti mulatory activity. Manipulation of cytokine production in DC could be a str atagem that has evolved in the retrovirus to avoid stimulation of cellular responses.