T-cell induced pathogenesis in HIV: bystander effects and latent infection.
The progress of HIV is accompanied by the infection and decline of the population of CD4+ cells. This reduction in cells results from both cytolytic influences of the virus and virus-specific cytotoxic T-cell (CTL) responses. We seek to characterize the extent of CD4+ reduction caused by HIV-specific CTLs at equilibrium. Here we show that intermediate levels of cytotoxic killing 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 response are made worse by a slow immune response. Bystander effects in which uninfected cells are thought to be eliminated by non-specific CTL activation lead to small or negligible reductions in uninfected CD4+ cells. Latently infected cells containing pro-viral DNA and which become activated at a constant rate ensure that the immune response is more effective for a larger range of CTL activities and reduces T-cell associated pathology.
Krakauer
D C
DC
Institute of Advanced Study, Princeton, NJ 08540, USA. krakauer@ias.edu
Nowak
M
M
D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D006678:HIV / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D018448:Models, Immunological; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D017735:Virus Latency