Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo.
We investigated the antigen specificity and presentation requirements for inactivation of T lymphocytes in vitro and in vivo. In vitro studies revealed that splenocytes treated with the crosslinker 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (ECDI) and soluble antigen fragments failed to stimulate significant proliferation by normal pigeon cytochrome c-specific T cell clones, suggesting that the chemical treatment inactivated full antigen presentation function. However, T cell clones exposed to ECDI-treated splenocytes and antigen in vitro were rendered unresponsive for at least 8 d to subsequent antigen stimulation with normal presenting cells. As predicted by the in vitro results, specific T cell unresponsiveness was also induced in vivo in B10.A mice injected intravenously with B10.A, but not B10.A(4R), splenocytes coupled with pigeon cytochrome c via ECDI. The antigen and MHC specificity of the induction of this T cell unresponsiveness in vitro and in vivo was identical to that required for T cell activation. These results suggest that nonmitogenic T cell recognition of antigen/MHC on ECDI-modified APCs results in the functional inactivation of T cell clones.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D002234:Carbodiimides / Q000494:pharmacology*; D002999:Clone Cells / Q000276:immunology; D010856:Columbidae; D003432:Cross-Linking Reagents; D003574:Cytochrome c Group / Q000276:immunology; D005022:Ethyldimethylaminopropyl Carbodiimide / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D007700:Kinetics; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D002234:Carbodiimides; D003432:Cross-Linking Reagents; D003574:Cytochrome c Group; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D005022:Ethyldimethylaminopropyl Carbodiimide