Immunological memory and acquired immunodeficiency syndrome pathogenesis

Infection with the human immunodeficiency virus results in profound perturb ations in immunological memory, ultimately resulting in increased susceptib ility to opportunistic infections and acquired immunodeficiency syndrome (A IDS). We have used rhesus macaques infected with the simian immunodeficienc y virus (SIV) as a model to understand better the effects of AIDS virus inf ection on immunological memory. Acute infection with SIV resulted in signif icant deficits in CD4(+) helper responses to cytomegalovirus (CMV) as well as CMV-specific cytotoxic T-lymphocyte and neutralizing antibody responses. Reactivation of CMV was associated with high levels of SIV replication and suppression of both T-helper and cytotoxic responses to CMV. We have also studied the effects of SIV infection on T-cell turnover in non-human primat es. T-cell turnover was evaluated using the nucleoside analogue bromodeoxyu ridine (BrdU) in combination with five-colour flow cytometric analysis. T c ells in normal animals turned over at relatively rapid rates, with memory c ells turning over more quickly than naive cells. In SIV-infected animals, t he labelling and elimination rates of both CD4(+) and CD8(+) BrdU-labelled cells were increased by two- to threefold compared with normal controls. Fu rther analysis of immunological memory in nonhuman primates should offer th e opportunity to extend immunological insights from murine models to the pa thogenesis and prevention of AIDS.