title: Anergy and suppression regulate CD4(+) T cell responses to a self peptide.
abstract: To examine the role of cognate peptide in establishing CD4(+) T cell tolerance, we have mated transgenic mice that express the major I-E(d)-restricted determinant (S1) from the influenza virus PR8 hemagglutinin (HA28 mice) with mice expressing a S1-specific T cell receptor (TS1 mice). Surprisingly, S1-specific CD4(+) T cells were not substantially deleted in TS1xHA28 mice; indeed, lymph node cells expressing the S1-specific TCR were as abundant in TS1xHA28 mice as in TS1 mice. The S1-specific T cells in TS1xHA28 mice were, however, impaired in their ability to respond to S1 peptide both in vitro and in vivo, and contained two distinct populations. Approximately half expressed a unique cell surface phenotype (CD25(hi)/CD45RB(int)) and had been anergized by the neo-self S1 peptide. The remainder responded normally to the S1 peptide if purified away from the anergic T cells, but their proliferation was suppressed when the anergic T cells were also present in unfractionated lymphnode cells or in mixed cultures. These findings establish that anergy and suppression are coordinated mechanisms by which autoreactive CD4(+) T cells are regulated and that anergic/suppressor CD4(+) T cells can develop in response to self peptides.
authors.affiliation: The Wistar Institute Philadelphia, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Jordan
authors.forename: M P
authors.initials: MP
authors.lastname: Riley
authors.forename: H
authors.initials: H
authors.lastname: von Boehmer
authors.forename: A J
authors.initials: AJ
authors.lastname: Caton
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D011948:Receptors, Antigen, T-Cell