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Blood, 15 January 2005, Vol. 105, No. 2, pp. 735-741.
Prepublished online as a Blood First Edition Paper on September 28, 2004; DOI 10.1182/blood-2003-11-3900.
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IMMUNOBIOLOGY
Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis
Anna Balandina,
Sandrine Lécart,
Philippe Dartevelle,
Abdelhadi Saoudi, and
Sonia Berrih-Aknin
From the Laboratoire de Physiologie Thymique, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 8078, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Service de Chirurgie thoracique, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Institut National de la Santé et de la Recherche Médicale U-563, Centre de Physiopathologie, Toulouse-Purpan, Toulouse, France.
Thymus-derived CD4+CD25+ regulatory T (Treg) cells are essential for the maintenance of immunologic self-tolerance. Despite their critical role in the active suppression of experimental autoimmune disorders, little is known about their involvement in human autoimmune diseases. Myasthenia gravis (MG) is a CD4+ T cell–dependent autoimmune disease and the thymus is assumed to be the initiation site. To identify possible defects in the Treg cells in MG, we analyzed CD4+CD25+ cells in thymi from patients with MG compared to those from healthy subjects. We found a normal CD4+CD25+ number but a severe functional defect in their regulatory activity together with a decreased expression of the transcription factor, Foxp3, which is essential for T-cell regulatory function. The phenotypic analysis of CD4+CD25+ thymocytes revealed an increased number of activated effector cells with strong Fas expression in patients with MG. However, whatever their level of Fas, CD4+CD25+ thymocytes from patients with MG remained unable to suppress the proliferation of responding cells, indicating that the impaired Treg cell function is not due to contamination by activated effector T cells. These data are the first to demonstrate a severe functional impairment of thymic Treg cells in MG, which could contribute to the onset of this autoimmune disease.
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