More recently, a large body of evidence has appeared that shows that NEF has many important effects of many cells of the immune system. Both exogenous and endogenous NEF down-regulates HLA-ABC molecules critical for the initiation of cytotoxic T lymphocyte (CTL) responses, thus impairing antigen presentation to HIV-specific CD8 lymphocytes. NEF and gp 120 also are able to down-regulate major histocompatibility complex class I (MHC-I) in dendritic cells (DCs) and introduction of exogenous NEF leads to up regulation of MHC-II molecules, thereby favoring CD4 T-cell activation. This step increases the “pool” of lymphocytes permissive to infection. However, endogenous NEF does not modulate MHC-II surface expression; rather it induces a loss of co-stimulation. These results underscore the pleiotrophic action of NEF. On one hand, exogenous NEF triggers ABC-mediated bystander T-cell activation, ensuring viral spread, while endogenous NEF induces a loss of co-stimulation, favoring immune evasion.