NSF Award
9219186
The objective of the proposed studies is to understand how T cell differentiation and function are regulated during development. Two different, but complementary approaches will be taken to investigate this issue thoroughly. First, the phenotypic and functional properties of peripheral T cells arising in vivo from defined populations of fetal or adult T cell precursors will be compared. Chimeric animals will be created in which differentiation occurs (a) in the adult thymus after intrathymic injection of precursor cells or (b) in the intact fetal thymus following transplantation under the host kidney capsules. These experiments will reveal, for the first time, whether the acquisition of immunocompetence is controlled by developmental changes in the T cell precursor population. The second approach will be to investigate the mechanisms underlying functional differences between neonatal and adult T cells. The roles of cytokines, cell types, and lymphokine gene expression in the differential lymphokine secretion patterns of neonatal and adult T cells will be examined. This will provide novel information on the biochemical and molecular events mediating neonatal immunoincompetence vs adult immunocompetence. Taken together, these studies will provide valuable new insights into the development of the T cell lineage. %%% Of central importance to understanding immunity is understanding how the ability to mount an immune response (immunocompetence) arises and is maintained during development. There is compelling evidence that developmental changes in the cells that give rise to the array of adult T-lymphocytes are important. At present, there is no clear understanding of the mechanisms controlling T-cell developmental changes. The goals of this project are to determine whether specific developmental changes in T-cell precursor populations control the acquisition of immunocompetence and to study the molecular and biochemical events responsible for functional differences between neonatal T cells which are not immunocompetent and adult T cells which are. This research should contribute important new information about the development of the immune system.
