People with primary progressive multiple sclerosis (pwPPMS) have a reduced number of memory and regulatory immune cells compared to healthy controls, according to a study published in Cells.

During the study, it was observed that pwPPMS had lower numbers of central memory (CM; CD45RACCR7+) T cells expressing CD4+ and CD8+ as well as a reduction in activated regulatory T cells (Tregs) expressing HLA-DR (CD45RAHLA-DR+) compared to age- and sex-matched healthy controls. No differences in B cells were observed.

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Higher percentages of the most differentiated natural killer (NK) cells expressing NKp46 were observed in pwPPMS compared to healthy controls. A higher number of NK T cells (NKT) expressing KIR3DL2/3 and NKp30 was also found in pwPPMS.

“Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity,” the authors said.

The study also found that disease severity, measured by the Expanded Disability Status Scale (EDSS), and years since diagnosis were related to changes in the percentages and numbers of immune cells, especially NK cells.

Using linear regression models, negative correlations were observed between higher EDSS scores and percentages of total NK cells, a number of total NK cells expressing NKG2A, and lower numbers of intermediately differentiated (CD56dimCD57) NK cells. The change in CD56dimCD57 NK cells was specific to those expressing the inhibitory receptors KIR2DL2/3, KLRG1, and/or NKG2A, as well as those expressing the activating receptor NKp46.

Time since diagnosis of PPMS was also correlated with NK cell changes. Longer time since diagnosis was related to lower numbers of immature NK cells, lower numbers of total NK cells, and CD56dimCD57 NK cells expressing the inhibitory NKG2A receptor. In addition to changes in NK cells, a long time since diagnosis was also negatively correlated with the number of activated HLA-DR+ Tregs.

During the study, 23 pwPPMS and 23 healthy controls were recruited from clinical sites in Portugal and Spain. The participants had to be at least 18 years of age and be naïve to MS disease-modifying treatments.


Canto-Gomes J, Da Silva-Ferreira S, Silva CS, et al. People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs. Cells. Published online January 29, 2023. doi:10.3390/cells12030439