T cells and costimulatory factors in myasthenia gravis

摘要: The autoimmune disease myasthenia gravis (MG) is characterized by muscle weakness due to a loss of acetylcholine receptors (AChR) at the neuromuscular end plate. Most MG patients have pathogenic antibodies directed against receptor. We provide further evidence that T cells are important for establishment and continuation disease. detected capable transferring mice in healthy twin sisters as well their affected two monozygotic pairs discordant MG. However, did not demonstrate cell responses AChR. A support importance maintaining shown successful treatment an patient with targeting CD25. This molecule expressed on activated cells. levels cells, serum IL-10 soluble costimulatory molecules sCD28, sCD80, sCD86 sCD152 decreased, suggesting normalization abnormally immune system. Costimulatory activation inhibition response. demonstrated reduced expression CD152 (cytotoxic lymphocyte associated antigen 4, CTLA-4) from patients. essential inhibit response, therefore might potential down-regulate ongoing reaction. observed G allele position +49 coding sequence 1 gene was increased activity, manifested IL-1β CD3CD28 thymoma more frequently had G/G genotype or allele, which could explain active response this genotype. factors CD28, CD80, CD86 also exist forms. concentrations sCD152, all recently been be different diseases, were one our studies we elevated correlated each other IL-6, IFN-γ. All four sCD25 persons, while only sCD80 In addition, confirmed results others demonstrating sICAM-1. produced recombinant form naturally occurring factor CD80. Recombinant capacity interact its natural ligands CD28 CD152. It preferentially bound it displayed immunosuppressive properties, activation, mixed reaction ability alter cytokine secretion balance vitro. effect vivo has clarified, but tempting speculate about future use protein diseases like summary, provided initiation maintenance MG, involved progression. LIST OF PUBLICATIONS thesis based following original articles, referred text Roman numerals: I. Kakoulidou M, Ahlberg R, Yi Q, Giscombe Pirskanen Lefvert AK. B repertoires twins gravis. J Neuroimmunol. 2004, 148 (1-2), pp 183-191 II. Wang XB, Qiu Huang DR, CDS1 promoter single nucleotide polymorphisms CTLA-4 human Genes Immun. 2002, 3, 46-49 III. Abnormal gravis: AT-rich sequence. 130 224-232 IV. Zhao X, Soluble relation markers Manuscript V. AK, XB. Human CD80 generated alternative splicing. binds inhibits activation. Submitted VI. Treatment using