A deficiency of regulatory T cells (Tregs) may be one of the immunological mechanisms responsible for the damage observed in secondary progressive multiple sclerosis (SPMS), according to a study published in International Immunology.

The study found that the percentage of Tregs positive for CD4, CD25, forkhead box protein P3 (FOXP3), and Helios markers (CD4+CD25+FOXP3+Helios+ Tregs) was lower in the peripheral blood of SPMS patients compared to that of healthy controls (0.19 ± 0.25 vs 0.38 ± 0.27, respectively; P =.01). The percentage of T cells positive for CD4+FOXP3+CD25+ was also lower.

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“The findings suggest that the deficiency of regulatory T lymphocytes in the peripheral blood of SPMS patients could lead to disease progression,” the authors said.

The authors said that the decrease of both cell types in peripheral blood could be related to impairment of the thymus and also the absorption of Tregs into inflamed tissues.

Significantly lower levels of Helios gene expression were also observed in the SPMS patients compared to the healthy controls (P =.002). The Helios gene regulates Treg functional stability and previous studies in mice have shown that Helios suppression leads to defective regulation and the development of autoimmunity. The authors suggested that the decreased Helios expression may contribute to disease progression in the SPMS patients.

“Helios gene expression decreased in these patients, raising the likelihood of functional impairments in Tregs. However, no correlation was seen between this gene’s expression and the duration of the disease,” the authors said.

A total of 50 Iranian participants were recruited for the study including 25 patients with SPMS and 25 healthy controls. Flow cytometry was utilized to find the percentage of CD4+CD25+FOXP3+Helios+ Tregs after the extraction of peripheral blood mononuclear cells from blood samples. Real-time PCR was used to determine Helios gene expression levels.


Tarighi M, Shahbazi M, Saadat P, et al. Decreased frequency of regulatory T cells and level of helios gene expression in secondary progressive multiple sclerosis patients: evidence about the development of multiple sclerosis. Int Immunopharmacol. Published online February 2, 2023. doi:10.1016/j.intimp.2023.109797