DONOR HEMATOPOIETIC CELL CHIMERISM AND ORGAN AND TISSUE TRANSPLANTATION AND AUTOIMMUNE TOLERANCE

摘要

Compositions and methods are provided for the achievement of organ and tissue transplantation and autoimmune tolerance using the infusion of living and/or deceased donor hematopoietic cells. The methods provided herein provide for conditioning with a plurality of doses of total lymphoid irradiation (TLI), and a single, very low dose of TBI (svldTBI), referred to herein as "TLI-svldTBI-ATG" or "TLI-svldTBI" depending on whether ATG is included. The combination of svldTBI and TLI specifically targets non-lymphoid-tissue resident memory immune cells. An in vitro manipulated donor cell composition is provided for use with the conditioning regimen, in which specific ratios of CD34+ and other hematopoietic stem cell and precursor cell populations are combined with defined doses of CD3+ T cells, and/or purified regulatory T cells (Treg) cells, invariant natural killer (iNK-T) cells, and/or CD8+ memory T cells.