The objective of these studies is to analyze the early steps of T cell development in order to search for possibilities to increase T cell production in the thymus. An increased production of thymocytes would be helpful in the treatment of AIDS or in other diseases that cause T cell loss. A monoclonal antibody was generated to immature T cell blasts. This antibody has a co-stimulatory effect on the proliferation of immature T cells and bone marrow cells. The antigen recognized by the antibody was purified to homogeneity, and its N-terminal sequence analysis showed that the antigen is the dipeptidyl peptidase DPPIV, a membrane associated proteolytic enzyme. The identification of DPPIV as a hematopoietic and T lineage activator opens new possibilities in the analysis of immature T cell proliferation. Switching T cell development towards the gamma/delta lineage would be beneficial in HIV infected young patients, since these cells lack CD4, the HIV receptor. In order to achieve this goal experiments were initiated that analyze the regulation of TcR gamma chain expression and rearrangement. Another possible way to modulate T cell development is to regulate the thymic colonization process. We are in the process of the characterization of a T cell precursor invasion model.
