title: Secretion of IFN-gamma and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse.
abstract: We report differences in the supramolecular organization of the immunologic synapse (IS) formed by resting and anergic human T cells with agonist peptide-loaded antigen-presenting cells (APCs). T cells reactive to influenza A hemagglutinin peptide or Fel d 1 peptide 4 were rendered both anergic and regulatory by incubation with high doses of agonist peptide in the absence of APCs. At the IS between resting T cells and peptide-loaded APCs, both CD3epsilon and CD3zeta initially accumulate within a ring or arc before redistributing within 30 minutes to single or multiple foci more central to the contact. In contrast, at synapses formed by anergized T cells, CD3epsilon and CD3zeta remained organized within an arc or ring and failed to redistribute centrally. However, intercellular communication between anergic human T cells and agonist peptide-loaded APCs was not a null event, since it triggered secretion of T-cell interferon gamma (IFN-gamma) but not, for example, interleukin 2 (IL-2). Thus, distinct organizations of CD3 at the T-cell IS correlate with different cytokine profiles; the mature IS formed by resting T cells correlates with their production of both IFN-gamma and IL-2, whereas the immature IS formed by anergic T cells seems able to facilitate IFN-gamma but not IL-2 production.
authors.affiliation: Division of Cell and Molecular Biology, South Kensington Campus, Sir Alexander Fleming Building, Imperial College, London, SW7 2AZ, United Kingdom.
authors.forename: Leo M
authors.initials: LM
authors.lastname: Carlin
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yanagi
authors.forename: Adrienne
authors.initials: A
authors.lastname: Verhoef
authors.forename: Esther N M
authors.initials: EN
authors.lastname: Nolte-'t Hoen
authors.forename: John
authors.initials: J
authors.lastname: Yates
authors.forename: Leanne
authors.initials: L
authors.lastname: Gardner
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lamb
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Dallman
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Davis
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D017635:Clonal Anergy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D018613:Microscopy, Confocal; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D007376:Interleukin-2; D007371:Interferon-gamma