The primary goal of the immunologic and virologic core laboratories is to provide an ongoing, high quality, standardized service facility to all projects of the AIDS-CSG. These laboratories will be responsible for maintaining an AIDS specimen bank for serially collected samples of serum and lymphocytes; performing T4 counts on a regular basis for all patients entered into the AIDS-CSG; performing HIV cultures; monitoring HIV infection by detection of viral antigen; providing in depth analyses of immunologic function for those patients entered into clinical trials, measuring such parameters as lymphocyte proliferative responses to mitogens and antigens, natural killer function, quantitative serum immunoglobulins, and profiles of antibody reactivity to specific HIV proteins. A basic research component within the core immunology and virology laboratories is proposed, making use of the collective resources which the AIDS-CSG provide. First, a progression of the virus-specific humoral antibody response has been reported in AIDS, with antibody against many viral components demonstrable early on during the asymptomatic periods, and loss of detectable antibody later with onset of disease. Do these early antibodies confer some measure of protection against the progression of HIV infection? We are proposing to sequentially isolate specific antibody populations (directed against p24, gp120/160, etc.) from the serum of asymptomatic seropositive individuals and test these isolated antibodies in functional assays of antibody-dependent cellular cytotoxicity and neutralization correlating these results with the clinical course. Second, it is known that one of the earliest immunologic defects in HIV infection is the inability to respond to a new specific antigen stimulus. Monoclonal antibody directed against the monomorphic T3 portion of the antigen receptor provides one signal for T cell activation. Therefore, are lymphocytes from individuals at various stages of HIV infection capable of activation via an anti-T3 mechanism and does this change with therapeutic intervention? This means of lymphocyte activation, shown to mimic activation by specific antigen, would allow the study of lymphocyte triggering while bypassing the antigen specificity of the T cell receptor.
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