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Published online 23 January 2006 doi:10.1084/jem.20050648
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 2, 359-370
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ARTICLE

 The immune paradox of sarcoidosis and regulatory T cells

Makoto Miyara1,2, Zahir Amoura2,3, Christophe Parizot1, Cécile Badoual4, Karim Dorgham1, Salim Trad1, Marianne Kambouchner5, Dominique Valeyre5, Catherine Chapelon-Abric2, Patrice Debré1,3, Jean-Charles Piette2,3, and Guy Gorochov1,3

1 Institut National de la Santé et de la Recherche Médicale (INSERM) U543, Immunologie A and 2 Internal Medicine Department, AP-HP Hôpital Pitié-Salpêtrière, 75013 Paris, France
3 Université Pierre et Marie Curie-Paris6, 75005 Paris, France
4 INSERM U255, Centre de Recherches Biomédicales des Cordeliers, 75006 Paris, France
5 Pneumology Department, AP-HP Hôpital Avicenne, 93000 Bobigny, France

CORRESPONDENCE Guy Gorochov: guy.gorochov{at}psl.aphp.fr

Sarcoidosis is characterized by extensive local inflammation (granuloma, cytokine secretion) associated with anergy (poor response to antigens in vitro and in vivo). We postulated that this paradoxical situation would correspond to a disequilibrium between effector and regulatory T lymphocytes (T reg cells). We show that CD4+CD25brightFoxP3+ cells accumulate at the periphery of sarcoid granulomas, in bronchoalveolar lavage fluid, and in peripheral blood of patients with active disease. These cells exhibited powerful antiproliferative activity, yet did not completely inhibit TNF-{alpha} production. Sarcoidosis is therefore associated with a global T reg cell subset amplification whose activity would be insufficient to control local inflammation. At the same time, peripheral T reg cells exert powerful antiproliferative activity that may account for the state of anergy. Altogether, these findings advance our conceptual understanding of immune regulation in a way that resolves the immune paradox of sarcoidosis and permit us to envisage a profound clinical impact of T reg cell manipulation on immunity.

Abbreviations used: AC, accessory cell; AS, active sarcoidosis; BALF: Bronchoalveolar lavage fluid; T reg cell, regulatory T cell.

C. Parizot and C. Badoual contributed equally to this work.


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