title: Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells.
abstract: Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of cells. This paradigm predicts that synaptically secreted cytokines such as IFN-γ will preferentially signal to antigenic target cells contacted by the T cell through an immunological synapse. Despite its physiological significance, this prediction has never been tested. We developed a live-cell imaging system to compare the responses of target cells and nonantigenic bystanders to IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Both target cells and surrounding nontarget cells respond robustly. This pattern of response was detected even at minimal antigenic T-cell stimulation using low doses of antigenic peptide, or altered peptide ligands. Although cytotoxic immunological synapses restrict killing to antigenic target cells, the effects of IFN-γ are more widespread.
authors.affiliation: Department of Neurosurgery, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Nicholas Stephen Rennie
authors.initials: NS
authors.lastname: Sanderson
authors.forename: Mariana
authors.initials: M
authors.lastname: Puntel
authors.forename: Kurt M
authors.initials: KM
authors.lastname: Kroeger
authors.forename: Niyati S
authors.initials: NS
authors.lastname: Bondale
authors.forename: Mark
authors.initials: M
authors.lastname: Swerdlow
authors.forename: Niloufar
authors.initials: N
authors.lastname: Iranmanesh
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Maria G
authors.initials: MG
authors.lastname: Castro
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Lowenstein
mesh_terms: D000256:Adenoviridae; D000704:Analysis of Variance; D001253:Astrocytes / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins; D007091:Image Processing, Computer-Assisted; D054992:Immunological Synapses / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D008853:Microscopy / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D049452:Green Fluorescent Proteins; D007371:Interferon-gamma