THE EFFICIENCY OF ACUTE INFECTION OF CD4(-CELLS IS MARKEDLY ENHANCED IN THE SETTING OF ANTIGEN-SPECIFIC IMMUNE ACTIVATION() T)

Human immunodeficiency virus (HIV) disease is sub-Saharan Africa gener ally differs from that observed in the United States and other develop ed countries in that the risk of seroconversion after exposure is grea ter and the rate of disease progression to AIDS and death is faster. O ne theory that could in part explain this difference is the increased state of immune activation associated with a relatively high rate of p arasite infestation and other infections among inhabitants of these re gions. Using a model based on the cellular microenvironment of lymphoi d organs, the role of exposure to HIV during a state of antigen-specif ic immune activation was investigated. Dendritic cells and CD4(+) T ce lls are the major cellular components of the paracortical region of ly mphoid tissue, the primary site of HIV replication. We analyzed cocult ures of HIV-pulsed dendritic cells that had matured in the presence of tetanus toroid and CD4(+) T cells before and after inducing an antige n-specific response by in vivo immunization with tetanus toxoid. Durin g antigen-specific immune activation, 100 times less HIV was needed to initiate a productive infection. These findings provide a model syste m to further delineate the relationship between immune activation and the propagation of HIV infection and suggest a mechanism for the epide miologic observations of an increased ease of developing HIV infection and faster progression for HIV disease in geographic areas where immu ne activation is prevalent.