Induction of central tolerance by mature T cells.
Induction of immunological tolerance is highly desirable for the treatment and prevention of autoimmunity, allergy, and organ transplant rejection. Adoptive transfer of MHC class I disparate mature T cells at the time of reconstitution of mice with syngeneic bone marrow resulted in specific tolerance to allogeneic skin grafts that were matched to the T cell donor strain. Mature allogeneic T cells survived long-term in reconstituted hosts and were able to re-enter the thymus. Analysis of T cell development using transgenic mice expressing an alloantigen-reactive TCR revealed that expression of allogeneic MHC class I on adoptively transferred mature T cells mediated negative selection of developing alloreactive T cells in the thymus. Thus, mature allogeneic T cells are able to mediate central deletion of alloreactive cells and induce transplantation tolerance without the requirement for any other alloantigen-expressing cell type.
Tian
Chaorui
C
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129.
Bagley
Jessamyn
J
Forman
Daron
D
Iacomini
John
J
D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D016026:Bone Marrow Transplantation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics; D006650:Histocompatibility Testing; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011828:Radiation Chimera; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods; D023001:Transplantation Tolerance / Q000235:genetics
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse