HIV infected cells of the immune system and by depletion or alteration of the function of these cells causes a progressive immunodeficiency. Host recovery is dependent on the reconstitution of immune function as well as the elimination of virus. Because of difficulties in measuring immunological responses in a developing immune system and limited quantity of blood samples, little is known about the immunologic abnormalities which occur in the HIV positive pediatric population. With this current limitation of basic knowledge, it is not possible to predict effective reconstructive therapy. It has been demonstrated with other immune-based diseases that specific cytokine patterns, identifying specific TH-1 or TH-2 CD4 """"""""T helper"""""""" cell activity, are associated with protection and/or recovery. In addition, we have identified a monocyte marker, tissue factor, which correlates with disease progression and prognosis. to address the need for immunological disease markers in children, we propose to measure cytokine expression and cell proliferation in immune cells and correlate these parameters with HIV expression. HIV positive children and age matched controls will be monitored longitudinally, before and during therapy, as well as analyzed cross-sectionally by disease stages P0, P1, and P2. Cytokine expression in lymphocytes, following a 4 hour stimulation with PHA, will be measured by quantitative RNA PCR. In this way, abnormal patterns of individual cytokines can be determined and specific TH-1/TH-2 patterns can be identified. The antigen- and mitogen-driven proliferative response of isolated CD4 cells will be evaluated and compared to cytokine expression and production. Monocyte function will be monitored by measuring the expression of tissue factor and other monokines following LPS- stimulation. In conjunction with these immune cell evaluations, the level of cellular HIV RNA expression will be measured by quantitative RNA PCR. Our research goals are to define in the pediatric population: 1) components of immunity that reflect a positive response to therapy and; 2) impaired aspects of the immune response that can be targets for reconstructive immune therapy.
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