It is well recognized that the Acquired Immunodeficiency Syndrome (AIDS) is caused by a leukotrophic virus (human immunodeficiency virus, HIV) which is primarily transmitted through sexual contact. Control of the AIDS epidemic may depend on understanding fundamental mechanisms underlying sexual transmission of this disease. The proposed studies are designed to provide information concerning factors in human male reproductive tissues and semen that may play a role in AIDS infection and transmission. They address the following questions: Where do potential HIV host cell (CD4 (T4+) lymphocytes, monocytes/macrophages, other T4+ cells) reside in male reproductive tissues? Are viable HIV host cells present in semen of normal men? Are there cofactors such as infection or autoimmunity that affect their numbers? Are T4+ lymphocytes activated by factors such as sperm or infectious organisms in the reproductive tract? (This is significant because activation is thought to trigger HIV replication.) Does seminal plasma affect leukocyte viability, DNA synthesis, protein synthesis or surface antigen expression? Are potential HIV host cells attracted by seminal plasma chemotactic factors? We propose to: 1) use monoclonal antibodies to the T4 antigen (HIV receptor) and other lymphocyte and monocyte markers to identify potential HIV host cells and immunologic mediators in male reproductive tissues and semen; 2) use monoclonal antibodies directed against T cell activation markers to assess T cell activation in male reproductive tissues and semen; 3) compare profiles of resting and activated T4+ lymphocytes and other immunologic cells in semen from normal men to those in semen of men with clinical histories of venereal infection or sperm immunity; 4) use sensitive viability dyes and radiolabelled nucleic acid and amino acid precursors to study effects of human seminal plasma on leukocyte viability, DNA and protein synthesis; 5) use monoclonal antibodies to T4 and major histocompatibility antigens in quantitative radioimmunoassay and immunoprecipitation studies to determine if human seminal plasma affects the expression and structure of leukocyte surface markers important for HIV infection or immune defense mechanisms; and 6) use leukocyte separation techniques and monoclonal antibody reagents to identify leukocyte cell types that are attracted by human seminal plasma chemotactic factors in vitro.
