| Backgroud and Objectives:Myasthenia gravis (MG) is an autoimmune disease mediated by anti-acetylcholine receptor autoantibodies which cause muscle weakness by imparing neuromuscular transmission. The thymus has been thought to play a crucial role in the pathogenesis of MG because that 80%-90% of the patients with MG have abnormal pathological changes in thymus such as hyperplasia and thymoma. Thymus is a central organ in which lymphocyte undergo a series of dynamic cellular events including positive selection and negative selection to differentiate and acquire self-MHC restriction and self-tolerance to maturate, then settle down in the peripheral immune organ such as speen and lymph node. If the structure and function of the thymus abnormalities ,it will change the normal selection process to result in the fact that autoreactive T cell can not be cleared. The disequilibrium of central immune tolerance will lead to the occurrence of autoimmune diseases. Recent years,many studys find that myasthenia gravis is a T cell-dependent autoimmune disease according with the disequilibrium of cellular immunity.CD45 is a protein tyrosine phosphatase expressed on all hemopoietic cells which plays a crucial role in the function of T cell by dephosphorylate the Src-kinases. The expression of different CD45 isoforms generated by alternative splicing of variable exon 4,5 and 6 depends on their state of maturation and whether or not they have previously been exposed to antigen. Different isforms of CD45 display a different ability to support T cell activation and the expression of CD45 is essential for antigen-induced activation of T lymphocytes.This study was undertaken to investigate the development of T cell subsets and the function of CD45 in hyperplastic thymus of MG. For this purpose ,the expression of CD45RA,CD45RO,CD4 and CD8 in thymocyte were estimated by immunohistochemistry and flow cytometric analysis. RT-PCR and Real time PCR were used to detect the mRNA expression of CD45,CD69,Bcl-2 and CD28 in the hyperplastic thymus of patients with MG to explore the pathogenesis of myasthenia gravis.Methods:1. Immunohistochemistry were used to examine the expression of CD45RA and CD45RO in the thymus of 15 patients with MG and 10 controls.2. The expression of CD45RA,CD45RO,CD4 and CD8 on thymocytes of 15 patients with MG and 10 controls by flow cytometry.3. RT-PCR and Real time PCR were used to detect the expression of CD45,CD69,Bcl-2 and CD28 mRNA in the hyperplastic thymus of 7 patients with MG and 7 controls.Results:1. The expression of CD45RA was weakly positive in both of the thymus in the patients with MG and controls(p>0.05).The expression of CD45RO in the thymus of MG patients was significantly higher than that in controls(p<0.05).2. The expression of CD45RA in the thymus of MG patients was significantly lower than that in controls(p<0.01), but the expression of CD45RO in MG patients was significantly higher than that in controls(p<0.01). The double-negative(CD4-CD8-) thymocyte in thymus of MG patients had no significant change compare with controls(p>0.05).The double-positive thymocyte (CD4+CD8+) in thymus of MG patients was significantly higher than that in normal controls(p<0.05),and the single-positive thymocyte (CD4+CD8- orCD4-CD8+) in thymus of MG patients was significantly lower than that in normal controls(p<0.05).3. The expression of CD45,CD69,Bcl-2 and CD28 mRNA in the thymus of MG patients were 2.55,2.03,2.21,2.08 fold up-regulated respectively compare with controls (2-ΔΔC>2).Conclusions:1. The higher expression of CD45RO in the hyperplastic thymus of patients with MG may associate with the abnormal development of thymocyte subsets and it may involve in the pathogenesisi of myashthenia gravis.2. The activity of thymocytes in MG is enhanced and the overexpression of CD45 mRNA in the thymus of MG may play a role in the regulation of TCR signal transduction to express CD69 which promote the function of T cell. |
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