title: T-cell receptor antagonist modifies cytokine secretion profile of naive CD4+ T cells and their differentiation into type-1 and type-2 helper T cells.
abstract: A T-cell receptor (TCR) antagonist is an analog of a peptide ligand for TCR that inhibits T-cell responses to the original peptide. We investigated the effects of a TCR antagonist on cytokine secretion of naive CD4+ T cells and their differentiation into type-1 and type-2 helper T cells (Th1 and Th2) induced by stimulation with varying doses of an antigenic peptide. In the presence of a TCR antagonist peptide, proliferation of naive CD4+ T cells and antigen dose-dependent secretion of interferon-gamma, a typical Th1-type cytokine, by these cells was down-regulated. With respect to the secretion of interleukin-4 (IL-4), a typical Th2-type cytokine, the TCR antagonist raised the concentration of the antigenic peptide required to elicit maximal IL-4 production and, surprisingly, significantly increased the maximum level of IL-4 secretion. Similar effects induced by the TCR antagonist were observed on the Th1/Th2 differentiation of naive CD4+ T cells. These results clearly indicate that, for naive CD4+ T cells, a TCR antagonist has the potential to change the balance of Th1/Th2 cytokine secretion and even enhance Th2 responses.
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Takato-Kaji
authors.forename: Mamoru
authors.initials: M
authors.lastname: Totsuka
authors.forename: Wataru
authors.initials: W
authors.lastname: Ise
authors.forename: Megumi
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hachimura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaminogawa
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins; D015870:Gene Expression / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D016207:Cytokines; D050485:GABA Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin