The acquired immunodeficiency syndrome (AIDS) is almost certainly caused by a retrovirus called lymphadenopathy virus (LAV) or human T cell lymphotrophic virus (HTLV-III); however, the immunopathology of the disease is not well understood. It is clear that not all individuals that are infected with HTLV-III or that develop that AIDS-related complex (ARC) will develop AIDS. The premise of this proposal is that other immunological factors may be responsible for the transition of ARC to AIDS. In particular, we have shown that an expansion of T8+ suppressor/cytotoxic cells with the natural killer antigen Leu 7 occurs in some patients with ARC and that the T8+Leu7+ cell is the predominant cell remaining in patients with AIDS.
The first aim of this proposal is to determine the temporal relationship of T8+Leu7+ cellular expansion in patients with ARC in relation to other phenotypic and functional changes. Lymphocytic subpopulations will be determined using dual or triple-color flow cytometric techniques. Functional assays will include responses to mitogens, mixed lymphocyte responses, the production of polyclonal Ig and interleukin 2.
The second aim i s to determine the mechanisms responsible for T8+Leu7+ expansion using in vitro approaches that will determine: (a) the lineage of these cells, and (b) their functional abilities and the mechanisms responsible for induction. The final goal is to determine whether T8+Leu7+ expansion in ARC patients is significant in the progression of ARC to AIDS.
