MECHANISM OF DENDRITIC CELL DYSFUNCTION IN RETROVIRAL INFECTION OF MICE

Dendritic cells (DC) from mice infected with the murine retrovirus Rau scher leukaemia virus (RLV) are poor stimulators of allogeneic and syn geneic T cells and express lower, but still significant, levels of MHC class II. In this paper we further investigated the mechanism of the dysfunction of DC. DC from infected animals did not cause anergy of T cells during coculture for 3 or 6 days. They did not release a substan tial amount of soluble factors which could suppress T cell responses. The low T cell responses on stimulation using RLV-infected DC could be overcome by the addition of control DC. Pretreatment of these control DC with monoclonal antibody against MHC class II molecules completely blocked their ability to restore stimulation of T cells in the presen ce of infected DC. However, antibody against MHC class I or mismatched MHC class II molecules did not prevent restoration of function, The r educed labeling of surface MHC class II molecules previously reported was shown to reflect a loss in total class II molecules within the cel ls; MHC class I levels were unaltered by exposure to the virus. In DC from RLV-infected mice biosynthesis of MHC class II was decreased by a round 50% at the transcriptional level in comparison with beta-actin. Thus, the down-regulation of surface class II molecules observed in DC following RLV infection is a consequence of a specific block in its b iosynthesis and the failure of DC to stimulate T cells may be a direct consequence of the reduced class II levels. Since reduced stimulation by DC is also seen in HIV-1 infection in humans we speculate that a s imilar mechanism might operate in retroviral infection in man. (C) 199 6 Academic Press, Inc.