MANIPULATION OF THE IMMUNE-RESPONSE BY FOREIGN GENE-EXPRESSION IN THETHYMUS

Retroviral gene transfer vectors have been developed for optimal in vi vo gene therapy. ideally, these vectors should target gene expression specifically to selected tissues or organs. Our studies focus on the d evelopment of retroviral vectors for gene delivery to the thymus. The goal of these studies is to utilize thymic expression of exogenous gen es to manipulate the immune repertoire. We have characterized the sele ctive thymic tropism of a molecular clone of Gross murine leukemia vir us, GD-17, to thymic medullary epithelial cells using immunohistochemi cal staining and confocal microscopy. Specific expression of viral ant igens in the thymus lead to the induction of immunologic tolerance to GMuLV proteins. This tissue specific vector may thus be used to study the requirements of epithelial mediated tolerance induction, and provi de a more efficient tool for gene therapy.