title: Distinct biochemical signals characterize agonist- and altered peptide ligand-induced differentiation of naive CD4+ T cells into Th1 and Th2 subsets.
abstract: We have recently shown that altered peptide ligands influence differentiation of CD4+ T cells into Th1 and Th2 subsets. In the present study, we have examined the biochemical signals in naive CD4+ T cells after priming with altered peptide ligand (APL) that correlate with differences in cytokine expression. Although we observed zeta-chain phosphorylation in APL-stimulated cells, other signaling events such as ZAP70 and Lnk phosphorylation are not initiated. This altered pattern observed in the early phosphorylation events correlates with a distinct Ca2+ mobilization pattern that characterizes APL-stimulated cells. By changing the calcium signaling environment during T cell priming, we present data indicating that qualitative differences in calcium mobilization are associated with differentiation of naive CD4+ T cells into Th1- and Th2-like effector subsets.
authors.affiliation: Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Boutin
authors.forename: D
authors.initials: D
authors.lastname: Leitenberg
authors.forename: X
authors.initials: X
authors.lastname: Tao
authors.forename: K
authors.initials: K
authors.lastname: Bottomly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology / Q000378:metabolism; D007399:Interphase / Q000187:drug effects / Q000276:immunology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000819:agonists* / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D003574:Cytochrome c Group; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D002118:Calcium