CUTTING EDGE - INDUCTION OF ANTIGEN-SPECIFIC HYPORESPONSIVENESS BY TRANSPLANTATION OF HEMATOPOIETIC-CELLS CONTAINING AN MHC CLASS-I TRANSGENE REGULATED BY A LYMPHOCYTE-SPECIFIC PROMOTER

We explored a novel approach to tolerance induction by the transplanta tion of bone marrow (BM) cells (BMCs) that themselves do not express a foreign histocompatibility Ag, but which give rise to mature lymphocy tes that do so. Lines of transgenic (FVB) mice were generated that con tained an MHC class I D-d cDNA regulated by a CD2 promoter. Because th e CD2 promoter is lymphocyte-specific and activated relatively late in lymphocyte ontogeny, D-d is expressed on most mature lymphocytes in t he periphery but only on developing B cells in the BM of transgenic mi ce. Transgenic BMCs are tolerogenic and reproducibly engraft in nontra nsgenic mice using a conditioning regimen that is nonpermissive for th e engraftment of conventional (MHC promoter) D-d-transgenic BMCs, Engr afted BMCs generate transgene-expressing lymphocytes and confer a stat e of Ag-specific hyporesponsiveness on the host that is primarily attr ibutable to a peripheral mechanism. The strategies by which tolerance can be optimized in this system are discussed.