FAILURE OF T-CELL HOMEOSTASIS PRECEDING AIDS IN HIV-1 INFECTION

We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4(+) or CD8(+) phenotype ('blind' T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4(+) T cells and increase in CD8(+) T cells) in homosexual men with incident human immunodeficiency virus, type 1 (HIV-1), infection who remained free of acquired immunodeficiency syndrome (AIDS) for up to eight years after seroconversion. In contrast, seroconverters who developed AIDS exhibited rapidly declining T cells (both CD4(+) and CD8(+)) for approximately two years before AIDS, independent of the time between seroconversion and AIDS, suggesting that homeostasis failure is an important landmark in HIV disease progression. Given the high rate of T-cell turnover in HIV-1 infection, blind T-cell homeostasis may contribute to HIV pathogenesis through a CD8(+) T lymphocytosis that interferes with regeneration of lost CD4(+) T cells.