Macaque models for early immunosuppression and T cell loss during acute immunodeficiency virus infections

The interval of acute infection with immunodeficiency viruses is critically important for determining the long-term rate of disease progression. The s teps of initial infection, systemic dissemination, and explosive replicatio n of pathogenic SIV or SHIV in macaques are being mapped to show the mechan isms responsible for remodeling host immunity, for establishing the persist ent infection, and for promoting disease progression. Here, we describe rec ent studies on two ways in which CD4(+) T cell populations are depleted dur ing acute infection. Initially, we discuss recent work on the mechanisms fo r CD4(+) T cell-mediated, MHC-unrestricted cytolysis. This mechanism shows how even soluble viral antigens such as the envelope glycoprotein, can prim e CD4(+) lymphocytes to be both effector and target cells in an unrestricte d cytolysis mechanism. The consequence of unrestricted cytolysis is a more rapid destruction of the CD4(+) T cell population. Secondly, we discuss the broader issue of T cell hyperactivation during acute infection. Inappropri ate activation of this lymphocyte population renders cells susceptible to a ctivation induced cell death and also increases the rate of virus replicati on. Macaque immunization studies have shown a clear role for extracellular Tat in hyperactivation. These two mechanisms, unrestricted cytolysis and T cell hyperactivation, are components of the acute infection that remodel ho st immunity and dictate the rate of progression to AIDS.