MURINE RETROVIRUS INDUCES DEFECTS IN THE FUNCTION OF DENDRITIC CELLS AT EARLY STAGES OF INFECTION

The infection and function of lymph node dendritic cells (DC) were ana lyzed at different time points of Rauscher leukemia virus infection in mice (3, 7, 14, and 21 days). Infection of DC was apparent after 3 da ys and significant infection (1-10% of the DC population) was document ed after 7 days. DC from infected mice as early as 3 days postinfectio n had a reduced ability to stimulate allogeneic normal T cells in the mixed lymphocyte reaction. T cells did become infected during the cocu lture but block of cross-infection of T cells by zidovudine did not ab olish the inhibitory effect. Other DC-dependent responses were also re duced on infection including DC-stimulated responses to influenza viru s. ConA and PMA induced an increase in [Ca2+](i) level in DC from cont rol mice. A low baseline level of [Ca2+](i) in DC from infected mice a nd reduced calcium mobilization upon ConA stimulation was found at all periods of infection. Ultraviolet-inactivated Rauscher leukemia virus failed to provoke significant changes in DC function in vivo. Six or 7 days after RLV infection DC expressed lower levels of Ia(d) but not H2D(d) molecules in parallel with lower expression of some adhesion mo lecules (CD18, CD54, CD44). No differences in expression of B7 surface antigen between control and infected mice were obtained. We did not f ind any evidence for the induction of apoptosis of naive syngeneic or allogeneic T cells by infected dendritic cells. The changes in DC func tion may have implications for the pathogenesis of retroviral infectio ns including HIV infection. (C) 1994 Academic Press, Inc.