Dynamics of Tolerance induction by B‐cell delivered Gene Therapy

Induction of central deletional T cell tolerance by gene therapy.

Transgenic mice expressing an alloreactive TCR specific for the MHC class I Ag K(b) were used to examine the mechanism by which genetic engineering of bone marrow induces T cell tolerance. Reconstitution of lethally irradiated mice with bone marrow infected with retroviruses carrying the MHC class I gene H-2K(b) resulted in lifelong expression of K(b) on bone marrow-derived cells. While CD8 T c...

Tolerance by Gene Therapy Induction of Central Deletional T Cell

Induction of B-cell tolerance by retroviral gene therapy.

The primary immunologic barrier to overcome before clinical xenotransplantation can be successful is rejection mediated by preformed natural antibodies in the host, directed toward a single carbohydrate epitope Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) present on porcine tissue, encoded for by the enzyme glucosyltransferase UDP galactose:beta-D-galactosyl-1, 4-N-acetyl-D-glucosaminide alpha(1-3)...

Tolerance induction by lentiviral gene therapy with a nonmyeloablative regimen.

Antibodies (Abs) directed at the Gal alpha1,3Gal beta1,4GlcNAc-R (alphaGal) carbohydrate epitope initiate xenograft rejection. Previously, we have shown that bone marrow transplantation (BMT) with lentivirus-mediated gene transfer of porcine alpha1,3 galactosyltransferase (GalT) is able to induce tolerance to alphaGal-expressing heart grafts following a lethal dose of irradiation. Here we show ...

Induction of T-cell tolerance to an MHC class I alloantigen by gene therapy.

Induction of immunologic tolerance to alloantigens is a major goal in the field of transplantation. Here, we demonstrate that efficient transduction and expression of a retrovirally transduced major histocompatibility complex (MHC) class I gene (H-2K(b)) in bone marrow (BM)-derived cells, resulting in a permanent state of hematopoietic molecular chimerism, induces stable tolerance to the transd...