Dysregulation of suppressive and migratory markers on Tregs have been linked to the pathogenesis of both MS and MG. For example, genetic abnormalities have been found in Treg suppressive markers CTLA-4 and CD25, while others have shown a decreased expression of FoxP3 and IL-10.
Myasthenia gravis (MG) is an autoimmune disorder in which CD4(+)CD25(+) FOXP3(+)regulatory T cells (Tregs) are thought to play important roles in driving the ongoing autoimmune response.
Down-regulation of miR-145 expression was confirmed in PBMC and CD4+CD25- T cells (T effector cells) from both EAMG rats and MG patients by real-time PCR.
We observed that both hyperplastic thymi with OMG or GMG expressed significantly higher levels of CD25 than those with non-MG (P = 0.007 and 0.001, respectively).
Furthermore, the CXCL13 expression in type AB thymoma patients with GMG was higher than those with Non-MG (P=0.003).There were no differences among expressions of CD4, CD25, Foxp3, and CXCL13 in type A and B3 thymoma patients, regardless of with OMG, GMG or Non-MG.
In this study, we used surface CD4, CD25(high), and CD127(low/-) expression to isolate a relatively pure population of Tregs, and established that there was no alteration in the relative numbers of Tregs within the peripheral T cell pool in MG patients.
Although the underlying molecular basis for the reduced expression of FoxP3 in CD4(+)CD25(+) Tregs from MG patients remains unknown, this study provided a potential target for MG therapy.
Thus, our results suggest that the suppression of myasthenia gravis-associated T cell responses exerted by the dual APL is mediated by the CD4+CD25+ immunoregulatory T cell function via TGF-beta or cytotoxic T lymphocyte-associated antigen 4, which further stimulate a cascade of events that up-regulates apoptosis.
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.