EFFECTS OF MURINE LEUKEMIA VIRUSES ON THE FUNCTION OF DENDRITIC CELLS

In asymptomatic human immunodeficiency virus-1 infection T cells respo nd normally to allogeneic dendritic cells (DC), but DC show reduced st imulatory capacity. By contrast in HTLV-1 infection no significant cha nges in allogeneic stimulation were seen but DC-stimulated activity of autologous T cells. In seeking animal models relevant to these diseas es the effects of two murine leukemia retroviruses, Rauscher leukemia virus (RLV) and Moloney leukemia virus (MLV) on the function of dendri tic cells and T cells in a primary mixed leucocyte reaction have been tested. Treatment by RLV in vitro suppressed the ability of DC to stim ulate allogeneic T cells from healthy animals. MLV at the same concent ration did not significantly affect the ability of DC to stimulate all ogeneic T cells, but provoked considerable enhancement of the low leve l stimulation by DC in the syngeneic system. Similar results were obta ined following in vivo exposure to viruses. Two pieces of evidence sug gested that these effects were due to impairment of DC function and we re not operating through infection of T cells. Firstly, exposure of T cells directly to virus in vitro and in vivo before stimulation with u ntreated allogeneic DC caused no significant alteration in T cell acti vity. Secondly, the impact of murine leukemia virus on DC function was not abrogated when infected DC were added to normal T cells and cultu red in the presence of zidovudine. Treatment of DC by RLV caused a dec rease of cluster formation with allogeneic T cells. No statistically s ignificant influence of MLV was observed on cluster formation after 3- h of incubation in the allogeneic system. However, after 18-h incubati on MLV-treated DC formed fewer clusters with T cells than untreated DC , At the same time a stimulatory effect of MLV on DC cluster formation with syngeneic T cells was found. Considerable decrease was found in major histocompatibility complex class II antigen and LFA-1 receptor e xpression on the DC surface in mice infected by RLV. MLV induced no si gnificant changes. These mouse retroviruses can therefore cause change s in DC function similar to those already reported using human retrovi ruses and may provide models for studying their effects.