Activation of naive CD4+ T cells in vivo by a self-peptide mimic: mechanism of tolerance maintenance and preservation of immunity.
Intrathymic selection generates a peripheral repertoire of CD4(+) T cells with receptors that retain low affinity for self-peptide MHC complexes. Despite self-recognition, T cells remain tolerant even in the setting of microbial challenge and resultant costimulatory signals. We demonstrate here a novel mechanism for tolerance maintenance under conditions of self-recognition and strong costimulation. TCR engagement in vivo with a low-avidity peptide, as a mimic of self, provided with poly(I:C) (dsRNA) led to division of naive T cells that was dependent upon costimulatory signals; however, the dividing cells rapidly underwent deletion. By contrast, the surviving cells that were activated as evidenced by up-regulation of CD69 did not become effectors upon restimulation with the same ligand and maintained an effective response against agonist peptide. We suggest TCR engagement with self-peptide MHC complexes promotes tolerance maintenance during pathogen challenge, while preserving efficient reactivity for subsequent encounter with foreign Ags.
Choi
Jin-Young
JY
Section of Rheumatology, Yale School of Medicine, New Haven, CT 06520, USA.
Craft
Joe
J
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D007108:Immune Tolerance; D007109:Immunity; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001324:Autoantigens; D037181:Lectins, C-Type; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens