T-cell induced pathogenesis in HIV: bystander effects and latent infection

The progress of HIV is accompanied by the infection and decline of the popu lation of CD4+ cells. This reduction in cells results from both cytolytic i nfluences of the virus and virus-specific cytotoxic T-cell (CTL) responses. We seek to characterize the extent of CD4+ reduction caused by HIV-specifi c CTLs at equilibrium. Here we show that intermediate levels of cytotoxic k illing of infected cells can be inferior to both strong and weak or absent immune responses. We further show that the deleterious effects of the CTL r esponse are made worse by a slow immune response. Bystander effects in whic h uninfected cells are thought to be eliminated by non-specific CTL activat ion lead to small or negligible reductions in uninfected CD4+ cells. Latent ly infected cells containing pro-viral DNA and which become activated at a constant rate ensure that the immune response is more effective for a large r range of CTL activities and reduces T-cell associated pathology.