alexa Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis.
Immunology

Immunology

Rheumatology: Current Research

Author(s): Balandina A, Lcart S, Dartevelle P, Saoudi A, BerrihAknin S

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Abstract 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.
This article was published in Blood and referenced in Rheumatology: Current Research

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