Journal
BLOOD
Volume 105, Issue 2, Pages 735-741Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-11-3900
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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 Fast 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. (C) 2005 by The American Society of Hematology.
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