Abnormalities of immune regulation in human immunodeficiency virus infection

The severe depletion of CD4+ T cells is the most obvious and dramatic immunologic event that occurs in individuals infected with the human immunodeficiency virus (HIV) type 1 during development to AIDS. Nevertheless, a complex and sequential pattern of loss of T-helper cell (TH) function can occur years before development of AIDS symptoms. Such suppression could be due to immunosuppressive factors that are either products of HIV, such as gpl20 and tat, or HIV-induced immunoreg-ulatory cytokines such as transforming growth factor-β and IL-10. Recent data suggest that multiple and independent immunosuppressive factors, including gpl20-induced suppression and IL-10, are responsible for the loss of TH function seen in HIV-infected individuals before development of symptoms. The same TH functional abnormalities observed in adult patients are also seen in pediatric cases. Pediatric cases of HIV infection present some unique problems, however, in that one needs to be able to distinguish between HIV-induced suppression of TH function and the absence of TH function that is due to lack of maturation or immunologic priming.