Immunopathogenic mechanisms of HIV infection.

A complex array of multiphasic and multifactorial immunopathogenic mechanisms are involved in the establishment and progression of human immunodeficiency virus (HIV) disease. After primary infection, acute viremia occurs with wide dissemination of HIV. During this early viremic phase, the virus is trapped within the processes of follicular dendritic cells in the germinal centers of lymphoid tissue. Also, during this phase of primary infection, some patients show major expansions of certain subsets of CD8+ T cells that are identified by the expression of a particular variable region of the beta chain of the T-cell receptor. These expansions are manifestations of responses to HIV that may be important in controlling the progression of HIV infection. In addition, inappropriate immune activation and elevated secretion of certain proinflammatory cytokines occur during HIV infection; these cytokines play a role in the regulation of HIV expression in the tissues. Infection of progenitor cells in bone marrow and the thymus contribute to the lack of regeneration of immunocompetent cells. Dendritic cells are involved in the initiation and propagation of HIV infection in CD4+ T cells. In studies of long-term nonprogressors - persons who have stable CD4+ T-cell counts and no HIV disease progression despite years of HIV infection - preserved lymph node architecture, low viral burden, and viral expression were found.