The mechanism of tolerance induction in thymus-derived lymphocytes; I. intracellular inactivation of hapten-reactive helper T lymphocytes by hapten-nonimmunogenic copolymer of D-amino acids.
Treatment of a p-azobenzoate (PAB) derivative of a copolymer of D-glutamic acid and D-lysine (D-GL) induced a profound state of unresponsiveness to PAB-reactive helper T lymphocytes generated in PAB-mouse gamma globulin (MGG)-primed mice. This unresponsiveness in T lymphocytes was specific for PAB-reactive cells, since the bacterial alpha-amylase-, keyhole limpet hemocyanin-, or ovalbumin-primed helper T lymphocytes were not suppressed by PAB-D-GL treatment. Taking advantage of the relative ease with which PAB-D-GL can induce specific unresponsiveness to helper T lymphocytes in an animal previously primed with PAB-MGG, it was possible to approach certain questions concerning the mechanisms of tolerance-induction and the fate of tolerant helper T lymphocytes in the PAB-D-GL model by utilizing a classical adoptive cell transfer systemmelimination of the possibility of carry-over of the tolerogen with cells or of the generation of suppressor cells as the result of PAB-D-GL treatment as an explanation of the suppression of helper T-cell activity strongly inplicates the existence of a central intracellular mechanism of specific tolerance on the helper T-cell level. The possibility that suppression of the activity of PAB-reactive helper T lymphocytes by PAB-D-GL reflects simple blocking of surface receptor molecules on T lymphocytes was ruled out as it was found that the helper activity of PAB-reactive cells was minimally suppressed even when PAB-D-GL was directly exposed in vitro to helper T lymphocytesmmoreover, the most conclusive evidence on te the tolerant state induced by in vivo exposure of primed T cells to PAB-D-GL. It appears, therefore, that specific tolerance induced by PAB-D-GL' TO PAB-reactive helper T lymphocytes is an example of irreversible inhibition of T-cell reactivity to antigen, reflecting yet to be determined events at the intra- and subcellular levels.
D000681:Amylases / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000276:immunology; D001391:Azo Compounds / Q000276:immunology; D001565:Benzoates / Q000276:immunology; D001666:Binding Sites, Antibody; D002352:Carrier Proteins / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism; D005620:Freund's Adjuvant; D005971:Glutamates; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007106:Immune Sera; D007108:Immune Tolerance; D007115:Immunization Schedule; D007116:Immunization, Passive / Q000379:methods; D008239:Lysine / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014357:Trypsin / Q000494:pharmacology; D005719:gamma-Globulins
D001391:Azo Compounds; D001565:Benzoates; D002352:Carrier Proteins; D005971:Glutamates; D006241:Haptens; D007106:Immune Sera; D010455:Peptides; D005719:gamma-Globulins; D003165:Complement System Proteins; D005620:Freund's Adjuvant; D006433:Hemocyanins; D000681:Amylases; D014357:Trypsin; D008239:Lysine