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Analyse de la spécificité antigénique des lymphocytes T auto-réactifs chez des patients atteints de la maladie de Vogt-Koyanagi-Harada.

Abstract : Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease affecting the eye, the meninges, theinner ear and the skin. The melanocytes are the cells common to the four affected tissues and areconsidered as the source of self-antigens. Our objective was to identify the antigens targeted bypotentially autoreactive CD4 T lymphocytes obtained from VKH patients. In preliminary experiments,we failed to isolate self-reactive lymphocytes in the blood of two patients. For a third patient with anuntreated uveomeningitidis, we isolated 107 T cell clones from his cerebrospinal fluid. Each of the107 T cell clones, among which ninety percent were CD4+, was tested for its ability to secretecytokines upon contact with autologous presenting cells loaded with either of the followingmelanocytic proteins: TRP1, TRP2, tyrosinase, gp100, Melan-A or KU-MEL-1. None of the 107 Tcell clones was able to specifically secrete TNF- , IFN- , IL-5, or IL-17 upon contact withautologous B cells loaded with the above-mentioned melanocytic proteins. Nine clones were Th17, asthey secreted IL-17 upon non-specific stimulation. Contrary to what would be implied from previousreports, activation of these CD4 T cell clones was not triggered by antigens derived from the sixmelanocytic proteins. This suggests that still undefined self-antigens are involved during the earlyphase of VKH disease.
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Sébastien Abad. Analyse de la spécificité antigénique des lymphocytes T auto-réactifs chez des patients atteints de la maladie de Vogt-Koyanagi-Harada.. Biochimie, Biologie Moléculaire. Université Paris-Nord - Paris XIII, 2014. Français. ⟨NNT : 2014PA132001⟩. ⟨tel-01235823⟩



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