INTRODUCTION
Immune activation is a characteristic feature of primary viral infections and is associated with marked expansion of CD8 T cells.1,2 In the case of human immunodeficiency virus (HIV), immune activation occurs during the chronic phase of the infection as well.
Not all of the immune activation is HIV specific, and “bystander activation” of multiple cell types has been documented.3,4 Although pathogen-specific immune activation is a necessary host requirement for self-protection, heightened generalized immune activation such as that which occurs with HIV has dire consequences. It is known to accelerate CD4 T cell depletion, increase viral replication, and decrease host survival.5-8 The cause for heightened immune activation in HIV infection is not fully understood and is attributed to many factors, including effects of virus gene products,9-16 coinfection with other pathogens,17,18 and reactivation of latent viruses.3,4 Increases in immune activation generally precede the inflection point of CD4 T cell depletion, and HIV-1 viral replication increases, suggesting a role for immune activation in the pathogenesis of HIV infection.Aberrant immune activation dampens HIV-specific immunity, and emerging data support this contention, although it has never been conclusively proven. One of the most compelling arguments for the adverse prognostic significance of immune activation may be made on the basis of observations in the sooty mangabeys, the natural hosts of simian immunodeficiency virus (SIV), and in rhesus macaques inoculated with SIV.19 Sooty mangabeys do not develop progressive disease despite ongoing viral replication, whereas rhesus macaques develop progressive acquired immunodeficiency syndrome (AIDS)-like disease. The major distinguishing characteristic between the mangabeys and macaques is the low level of markers of immune activation in the mangabeys and high- immune activation in the macaques. This chapter will discuss markers of immune activation, possible causes of immune activation, and its consequences, particularly in reference to events leading to activation-induced cell death (AICD) of CD4 and CD8 T cells.