Clonal deletion: a mechanism of tolerance in mixed bone marrow chimeras.
The mechanism of antigen-specific immunologic unresponsiveness which results from lethal irradiation and mixed (syngeneic-allogeneic) bone marrow cell (BMC) reconstitution is unknown. To determine whether clonal deletion is the mechanism of tolerance in this model, monoclonal antibody (Mab) RR-4-4, specific for a T-cell receptor (V beta 6) reactive against the minor alloantigen MLsa, was employed. Six-week-old B10 mice (H-2b, Mlsb, Thyl.2) were tolerized to AKR antigens (H-2k, Mlsa, Thyl.1) by whole body irradiation (950 R) and iv infusion of T-cell-depleted (TCD) B10 BMC + non-TCD AKR BMC. Chimerism and antigen-specific tolerance were documented by flow microfluorometry (FMF), skin grafting, mixed lymphocyte reaction, and cell-mediated lympholysis. When tolerant B10 mice (n = 15) had accepted AKR skin grafts for greater than 100 days, these animals were studied for the presence of host V beta 6+ T cells using Mab RR-4-4. FMF revealed that 0-5% of host (B10) lymph node and spleen cells from chimeras were V beta 6+ while 15-20% of lymph node and spleen cells from control B10 mice expressed V beta 6. These data demonstrate that clonal deletion occurs in the lethal irradiation-mixed reconstitution model as evidenced by the near total elimination of Mlsa-reactive V beta 6+ T cells and suggest that it maybe a mechanism responsible for tolerance in adult mice.
Yu
J C
JC
Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia 19104.
Webster
M
M
Fox
I J
IJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D001853:Bone Marrow / Q000528:radiation effects; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002678:Chimera / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D016038:Skin Transplantation / Q000276:immunology; D014185:Transplantation, Isogeneic
D000911:Antibodies, Monoclonal; D011947:Receptors, Antigen, B-Cell