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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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IMMUNOBIOLOGY

Secretion of IFN-{gamma} and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse

Leo M. Carlin, Kumiko Yanagi, Adrienne Verhoef, Esther N. M. Nolte-'t Hoen, John Yates, Leanne Gardner, Jonathan Lamb, Giovanna Lombardi, Margaret J. Dallman, and Daniel M. Davis

From the Division of Cell and Molecular Biology, South Kensington Campus, Imperial College, London; the Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College, London; the Department of Immunology, Hammersmith Campus, Imperial College, London, United Kingdom; and Translational Medicine and Genetics, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Greenford, Middlesex, United Kingdom.

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 CD3{epsilon} and CD3{zeta} 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, CD3{epsilon} and CD3{zeta} 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.


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