DEFECTIVE CELLULAR CONTROL OF ACTIVATED B LYMPHOCYTES IN THE ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS): ROLE OF LYMPHOTROPIC VIRUSES. AIDS is characterized by abnormalities in cellular immunity, especially a decrease in CD4+ T lymphocytes, leading to opportunistic infections and/or the development of neoplasms. Paradoxically, elevated serum IgG/A and spontaneous immunoglobulin- (Ig) secretion is seen in AIDS. The probable source of this B cell activation is exposure to lymphotropic viruses, such as Epstein- Barr virus (EBV), or the human immunodeficiency virus (HIV), the primary infectious agent in AIDS. When not effectively controlled, the growth of virus-activated human B cells can lead to the development of B cells lymphomas, as seen in immune- suppressed patients, including those with AIDS.
The specific aims of this project are to define the functional impairment in T cell- mediated regulation responsible for the excessive B cell activity seen in patients with AIDS, and, to deliniate the immunological mechanisms involved in the polyclonal activation of human B cells by HIV, including the role of T cells in regulating the growth of HIV-activated B lymphocytes.
These aims will be accomplished using the inhibition the virus-induced B cell activation, measured by Ig secretion or proliferation, as a marker for effective T cell suppression. The production of lymphokines involved in this process, such as interferon-gamma and -alpha, and interleukin-2 will also be examined. T cell subpopulations, isolated from patients with AIDS or HIV-infected healthy donors, will be tested. The role of different B and T cell subpopulations in the polyclonal B cell activation induced by HIV will also be examined. The long term goal is to define the defects in the regulation of in vivo virus-activated B cells in immune deficient individuals that allow chronically stimulated B cells to escape growth control at times form B cell lymphomas. Knowledge of these regulatory mechanisms will be of great valuable for the development of sound medical intervention in human immune deficiencies.
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