We previously demonstrated in cross-sectional analysis that, on average, children with MS exhibited increased frequencies and pro-inflammatory responses of particular Teff subsets, and diminished Treg function such that the balance between the Teff/Treg was dysregulated relative to children with monoADS. Of interest was whether this measure of Teff/Treg imbalance was a stable feature, or fluctuated over time, potentially associated with disease activity.

To assess whether abnormalities in effector (Teff) and regulatory (Treg) T cells in children with pediatric-onset multiple sclerosis (MS) as compared to children with monophasic acquired demyelinating syndromes (monoADS), are a stable disease feature, or fluctuate over time.

Frequencies of CD4⁺CCR2⁺CCR5⁺ and CD8⁺CD161^highTCR-Vα7.2⁺ MAIT Teff subsets, and the ratios of Teff to Treg (CD4⁺CD25^hiCD127^lowFOXP3⁺) cells, were serially assessed in children with MS and monoADS, prospectively followed as part of the Canadian/CHOP Pediatric Demyelinating Disease Study.

Children with MS (n=14) harbored increased frequencies of CD4⁺CCR2⁺CCR5⁺ and CD8⁺CD161^highTCR-Vα7.2⁺ MAIT Teff cells (p=0.021, and p=0.008, respectively), yet deficient Treg suppressive capacity (p=0.041), including diminished capacity to suppress the implicated Teff (p=0.01), compared to children with monoADS (n=7). In turn, the implicated Teff of MS patients were relatively resistant to suppression by normal Tregs (p=0.008). An abnormal Teff/Treg ratio at the individual level best distinguished MS children from controls (p<0.001). In a subset of serially studied children (n=10), Teff/Treg ratios of the individual children were relatively stable over a 3-5 year period, whether they had MS or monoADS.

Abnormalities in the Teff/Treg ratios distinguish children with MS from children with monoADS. These ratios tend to be relatively stable over time consistent with an intrinsic property of chronic immune dysregulation, which does not seem to be related to clinical disease activity.