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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3874-3879.
Prepublished online as a Blood First Edition Paper on August 11, 2005; DOI 10.1182/blood-2005-03-0996.
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Submitted March 11, 2005
Accepted August 4, 2005
Secretion of IFN- and not IL-2 by anergic human T cells correlates with assembly of an immature immunological synapse
Leo M Carlin, Kumiko Yanagi, Adrienne Verhoef, Esther N Nolte-'t Hoen, John Yates, Leanne Gardner, Jonathan Lamb, Giovanna Lombardi, Margaret J Dallman, and Daniel M Davis*
Department of Biological Sciences, South Kensington Campus, Imperial College London, London, United Kingdom
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, United Kingdom
Department of Immunology, Hammersmith Campus, Imperial College London, London, United Kingdom
Translational Medicine and Genetics, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Greenford, Middlesex, United Kingdom
* Corresponding author; email: d.davis{at}imperial.ac.uk.
We report differences in the supramolecular organization of the immunological synapse (IS) formed by resting and anergic human T cells with agonist-peptide loaded antigen-presenting cells (APC). T cells reactive to influenza A haemagglutinin 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 APC. At the IS between resting T cells and peptide-loaded APC, both CD3 and CD3 initially accumulate within a ring or arc before redistributing within 30 min to single or multiple foci more central to the contact. In contrast, at synapses formed by anergized T cells, CD3 and CD3 remained organized within an arc or ring and failed to redistribute centrally. However, intercellular communication between anergic human T cells and agonist-peptide loaded APC was not a null event, since it triggered secretion of T cell IFN- , but not for example 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- and IL-2 whereas the immature IS formed by anergic T cells seems able to facilitate IFN- but not IL-2 production.
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