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-2 beta) to M16 (Lyt-2 alpha) 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-2 beta) to M16 (Lyt-2 alpha) 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041982-04
Application #
3182613
Study Section
Immunobiology Study Section (IMB)
Project Start
1985-07-01
Project End
1991-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Overall Medical
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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Chang, J F; Thomas 3rd, C A; Kung, J T (1991) Induction of high level IL-2 production in CD4+8- T helper lymphocytes requires post-thymic development. J Immunol 147:851-9
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Kung, J T; Thomas 3rd, C A (1988) Athymic nude CD4+8- T cells produce IL-2 but fail to proliferate in response to mitogenic stimuli. J Immunol 141:3691-6
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Fichtner, A T; Anderson, S; Mage, M G et al. (1987) Subpopulations of mouse Lyt-2+ T cells defined by the expression of an Ly-6-linked antigen, B4B2. J Immunol 138:2024-33