Lymphocyte alloantigenic challenge as a potential cofactor in HIV infection and progression to AIDS

A hypothesis is developed that circulatory exposure to alloantigens found on lymphocytes triggers a series of events leading to suppression of the cell-mediated arm of the immune system and, therefore, that such alloantigenic challenge can be an important cofactor promoting infection with the human immunodeficiency virus (HIV) and development of the acquired immunodeficiency syndrome (AIDS) following infection. The explanatory model that is developed is based in large part on current knowledge of the results of fetal lymphocyte alloantigenic challenge of the maternal immune system. It is our contention that the maternal response which leads to suppression of cell-mediated immunity is a mechanism promoting survival of the fetal "allograft," and that this mechanism is an evolutionary adaptation in humans and other placental mammals. We also hypothesize that circulatory exposure to these same alloantigens leads to an immunosuppressive state which enhances survival of HIV in an exposed individual and augments the immunosuppressive action of HIV in promoting progression to clinical AIDS. Findings from studies of individuals who are at risk for exposure to lymphocyte alloantigenic challenge and from HIV infected patients are reviewed and discussed in light of this hypothesis.