The long term goal of the proposed grant proposal is understand the role of the thymus in the development of distinct subpopulations of Lyt-2+ T cells as monitored by B4B2 (an antigen expressed by 30-40% of normal Lyt-2+ T cells and 95% of nude Lyt-2+ T cells) and V beta.8 (T cell receptor) antigen expression as well as a series of functional assays. The role of the thymus on the """"""""differentiation potential"""""""" of highly purified Lyt-2+ T cell subsets isolated from normal and athymic nude mice and on the development of Lyt-2+ T cell subpopulations from bone marrow precursors will be studies in a histocompatible in vivo C57BL/6 (Lyt-2b) into M16 (Lyt-2a) transfer system. Specifically, the following experiments will be carried out: 1. Characterization of Immune Functions of Lyt2+B4B2+ and Lyt2+B4B2- Cells Isolated form Normal Mice. 2. Characterization of Immune Functions of Lyt2+ T Cells Isolated form Athymic Nude Mice. 3. Using a Histocompatible in vivo C57BL/6 (Lyt-2b) into M16 (Lyt-2a) Transfer System to Establish the Role of the Thymus in the Development of Lyt2+B4B2+ and Lyt2+B4B2- T cells: Marker Studies. 4. Using a Histocompatible in vivo C57BL/6 (Lyt-2b) into M16 (Lyt-2a) Transfer System to Establish the Role of the Thymus in the Development of Lyt2+B4B2+ and Lyt2+B4B2- T cells: Functional Studies. Such an experimental approach is expected to provide valuable information in understanding the thymic influence on the development of Lyt-2+ T cell subsets and consequently provide clues to the relative contribution of the thymus and Lyt-2+ T cell subsets in the cause and treatment of diseases including cancer, acquired immunodeficiency syndrome and autoimmune disorders.
