Tilted Balance of T Cell Renewal in HIV-1 Infection

The cause of CD4+ T lymphocyte depletion in HIV-1 infection is still not understood. Over the past years, attention has been focused on the hypothesis of highly increased T cell turnover with subsequent exhaustion of the immune system. However, the rate of T cell destruction was reported to be relatively low and the modest increase in lymphocyte production to compensate for this loss is not likely to be able to exhaust the immune system. Therefore, other mechanisms must be involved in the pathogenesis of lymphocyte depletion in HIV-1 infection. Interference of HIV with the renewal capacity of the immune system provides another explanation for the observed gradual decline in CD4+ T cell numbers. It has been postulated that the regenerative capacity of the immune system is intrinsically slow and cannot be significantly increased. Moreover, HIV-1 was shown to be able to infect bone marrow and thymic tissues, thereby impairing de novo production of naïve T cells. The net result of a modestly increased T cell loss and a severely impaired capacity of the immune system to compensate for this deprivation is a gradual decline in T cell numbers. We here argue that in HIV-1 infection the balance between lymphocyte production and destruction is disturbed, ultimately leading to severe immunodepletion and development of AIDS.