T regulatory cells lacking CD25 are increased in MS during relapse

Abstract

Dysregulation of inflammatory responses is considered to be a key element in autoreactive immune responses. T regulatory cells (Tregs) are important to maintain self-tolerance and the role of CD4⁺CD25⁺FoxP3⁺ Tregs in autoimmunity has been extensively investigated. Recently, it was shown that Tregs in systemic lupus erythematosus lacked CD25 but were biologically functional. These data warrants for further investigation of CD25⁻ Tregs in human autoimmunity. We analyzed relapsing–remitting multiple sclerosis (MS) patients by multicolor flow cytometry for the expression of CD3, CD4, IL2R (CD25), FoxP3, and the IL7R (CD127). Further, the level of Tregs was compared in remitting and relapsing patients and correlated with disease duration. Patients in relapse exhibited higher levels of FoxP3-positive Tregs lacking CD25 compared to healthy controls (p < 0.05), indicating that Tregs attempt to restrain immune activity during relapse. The proportion of Tregs tended to be decreased with disease duration, while CD25⁺CD4⁺ and CD25⁺CD8⁺ effector T-cell proportions were elevated and positively correlated with overall disease duration (p < 0.05). In conclusion, while MS patients in remission have normal levels of Tregs of different phenotype, relapsing patients show an increased proportion of systemic CD25⁻ FoxP3⁺ Tregs. With time, the proportion of Tregs decrease while effector T cells expand.

Keywords::

• MS
• T regulatory cells
• T cells
• FoxP3
• CD25

Acknowledgments

The authors wish to acknowledge Jan Gravé at the Rudbeck Core Facility, Uppsala University, for Excellent Technical Advice.

Declaration of interest: This study was supported by grants from the Swedish Research Council and the Göransson Sandviken Fund. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.