It has been much debated as to whether CD4÷ T-cell depletion and the patbogenesis of AIDS is the result of direct cytolytic effects of human immunodeficiency virus (HIV), T-cell apoptosis by nonspecific activation, dysregulation of cytokine production, or autoimmunity. In this context, Roll Zinkernagel and Hans Hengartner discuss data from model infections with non-cytopatbic viruses. They suggest that HIV may cause immunosuppression, not by dire~ r cytolytic effects, but rather by a conventional virus-specific cytotoxic T-cell-mediated immunopathology.

Human AIDS has prompted intensive research efforts, both to understand human immunodeficiency virus (HIV) and the disease. Although the virus is being defined in increasing detail, the complexities of the disease process are still poorly understood 1-3. The most commonly invoked pathogenetic mechanisms leading to AIDS are:(1) HIV-induced cytolysis, either directly 4-6 or through fusion-induced syncytia formationT. 8; 12) HIV-induced autoimmune attack on host immune cellsn'2"~ nl; 13) T-cell apoptosis after overwhelming nonspecific stimulationn2. 13; and (4) HIV-induced dysregulation of cytokines 4, 1-~. This viewpoint article proposes a fifth possibility, that AIDS may be the consequence of immunopathological mechanisms resuirine