Over the past several years, our research has been primarily aimed at unraveling the steps involved in the maturation and differentiation of T cells from uncommitted stem cells to mature, functional T cells. This research has recently yielded the finding that there exists a stage of T cell maturation which precedes migration to the thymus, during which receptors for antigen are expressed on the cell (pre-T cell) surface. Experimental evidence from our lab, as well as elsewhere, indicate that receptor-ligand interaction at this stage of development produces functional deletion of such clones in a manner reminiscent of B cell clonal abortion. We wish to utilize these findings to produce a state of pre-T tolerance to alloantigenic determinants, with an eye toward eventual clinical applicability. We will investigate already established in vivo tolerization regimens to determine the nature and extent of pre-T cell involvement in the tolerance produced. Such tolerizing protocols will include neonatally induced tolerance as well as protocols which induce alloantigen to tolerance in adult animals. These experiments will at one allow us to refine our assays for pre-T cell deletion as well as contribute to our understanding of the mechanisms involved in the induction and maintenance of the allo-tolerant state. We will attempt to develop means by which pre-T cells can be removed from normal bone marrow in vitro and attempt to characterize these cells.
| Chervenak, R; Altazan, J D (1987) Influence of MHC on thymus repopulation following intrathymic transfer of mouse T-cell precursors. Cell Immunol 105:290-300 |
