Increased Expression of Lymphocyte Activation Gene-3 by Regulatory T Cells in Multiple Sclerosis Patients with Fingolimod Treatment

Abstract

Introductions Multiple sclerosis (MS) is associated with the failure of peripheral tolerance to self-antigens. Regulatory T cells (Tregs) play a pivotal role in regulating the immune system and inhibiting development of au roim mune diseases. Until now, the effects of fingolimod, an immunomodulator, on different lymphocyte subsets are not full understood. In this study, we evaluated how fingolimod affects lymphocyte subsets of patients with MS. Material and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 20 MS and 12 healthy subjects. The number of white blood cells (WBCs) was assessed using an automated cell counter system. Circulating CD4(+)cells, CD4(+)FoxP3(+)cells, and CD25(+) FoxP3(+) LAG-3(+) Tregs were analyzed by flow cytometry. LAG-3 expression on CD4(+) FoxP3(+) cells was also determined using flow cytometry. Results: Our data revealed that fingolimod had a suppressive effect on WBC number in MS patients (P=0.0001). Fingolimod statistically significantly reduced rare of CD4(+)cells (P=0.0005), while increased the rate of circulating CD4(+) Foxp3(+) cells (P=0.014) and LAG-3 expressing Tregs (P=0.004) in MS patients. Moreover, fingolimod enhanced LAG-3 expression on CD25(+)FoxP3(+) cells of patients with MS (P=0.04). Conclusion: Based on these findings, fingolimod can be considered as one of effective therapeutic approaches for increasing the number of Tregs and modulating abnormal immune responses in patients with MS.