The immune paradox of sarcoidosis and regulatory T cells
Makoto Miyara, Zahir Amoura, Christophe Parizot, Cécile Badoual, Karim Dorgham, Salim Trad, Marianne Kambouchner, Dominique Valeyre, Catherine Chapelon-Abric, Patrice Debré, Jean-Charles Piette, Guy Gorochov, Makoto Miyara, Zahir Amoura, Christophe Parizot, Cécile Badoual, Karim Dorgham, Salim Trad, Marianne Kambouchner, Dominique Valeyre, Catherine Chapelon-Abric, Patrice Debré, Jean-Charles Piette, Guy Gorochov
Abstract
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+CD25(bright)FoxP3+ 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.
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References
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