title: Circadian variation of the response of T cells to antigen.
abstract: Circadian clocks regulate many important aspects of physiology, and their disturbance leads to various medical conditions. Circadian variations have been found in immune system variables, including daily rhythms in circulating WBC numbers and serum concentration of cytokines. However, control of immune functional responses by the circadian clock has remained relatively unexplored. In this study, we show that mouse lymph nodes exhibit rhythmic clock gene expression. T cells from lymph nodes collected over 24 h show a circadian variation in proliferation after stimulation via the TCR, which is blunted in Clock gene mutant mice. The tyrosine kinase ZAP70, which is just downstream of the TCR in the T cell activation pathway and crucial for T cell function, exhibits rhythmic protein expression. Lastly, mice immunized with OVA peptide-loaded dendritic cells in the day show a stronger specific T cell response than mice immunized at night. These data reveal circadian control of the Ag-specific immune response and a novel regulatory mode of T cell proliferation, and may provide clues for more efficient vaccination strategies.
authors.affiliation: Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Fortier
authors.forename: Julie
authors.initials: J
authors.lastname: Rooney
authors.forename: Hugues
authors.initials: H
authors.lastname: Dardente
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Hardy
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labrecque
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cermakian
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology; D056926:CLOCK Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell; D056926:CLOCK Proteins