Tolerance induction as a multi-step process.
Tolerant T cells are characterized by their partial or full resistance to activation by antigen. We investigated whether tolerant T cells were still receptive to further tolerogenic signals. T cells expressing a transgenic T cell receptor (TCR) specific for the major histocompatibility complex (MHC) class I molecule Kb were deleted in mice carrying Kb but not in mice expressing the mutant Kb-molecule Kbm1 [TCR (H-2bm1 x k) mice]. These T cells were tolerant in vivo but could be activated in vitro by the Kb antigen. This in vitro reactivity was abolished after the tolerant T cells encountered Kb-positive cells that had been intravenously injected. Furthermore, in TCR (H-2bm1 x k) mice expressing Kb only on hepatocytes, no T lymphocytes bearing the transgenic TCR could be found in the periphery, indicating that the additional contact with Kb on hepatocytes led to deletion of the tolerant T cells. These findings demonstrate that tolerance induction can be a multi-step process.
Schönrich
G
G
Tumor Immunology Program, German Cancer Research Center, Heidelberg.
Alferink
J
J
Klevenz
A
A
Küblbeck
G
G
Auphan
N
N
Schmitt-Verhulst
A M
AM
Hämmerling
G J
GJ
Arnold
B
B
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D002999:Clone Cells; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D007108:Immune Tolerance; D008212:Lymphocyte Depletion; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016827:CD8 Antigens; D006183:H-2 Antigens; D011948:Receptors, Antigen, T-Cell