Immunologic Targets of HIV Infection: T Cells

One of the principal targets of HIV infection is the human peripheral blood CD4⁺ T cell, resulting in progressive CD4⁺ lymphocyte loss. Hypothesized mechanisms for this loss include apoptosis, cytolytic reactions, V-p gene deletion of the T-cell receptor (TCR) by superantigens, CD4⁺ lymphocyte syncytium formation, and autoimmune reactions. In adults with HIV infection, the critical decline in CD4⁺ lymphocyte number that heralds the onset of AIDS-defining conditions is well characterized, whereas in infants and children the critical level of CD4⁺ cells predisposing to the development of AIDS-defining conditions or mortality is not fully characterized, due to an incomplete knowledge of CD4⁺ lymphocyte number and changes with age in normal and HIV-infected children. In a prospective study of 317 infants born to HIV-infected women, early results show that the monthly change in absolute CD4⁺ lymphocyte number over a 3- to 9-month period in HIV-infected infants was - 109 cells/mm3 per month, at least double the rate of decline measured in HIV-noninfected infants in the study or that calculated from normal infants' values reported in the literature. In other clinical studies in HIV-infected infants and children, it was possible to study the effect of low CD4⁺ cell counts on clinical status and mortality. In HIV-infected pediatric patients younger than 1 year, it was possible to correlate low CD4⁺ cell number with advanced disease status (CDC pediatric class P-2). It was also possible to correlate extremely low CD4⁺ cell counts (<200 cells/mm³) in HIV-infected children with a significant risk of mortality within the next 3 months of life. Sequential CD4⁺ cell analysis of HlV-high-risk infants will delineate the rate of HIV-related decline in CD4⁺ cells, thus facilitating the diagnosis of HIV infection and aiding in identification of HIV-infected children at high risk of disease progression or death.