Altered regulatory T-cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

Anderson P Jones; Stephanie Trend; Scott N Byrne; Marzena J Fabis-Pedrini; Sian Geldenhuys; David Nolan; David R Booth; William M Carroll; Robyn M Lucas; Allan G Kermode; Prue H Hart

doi:10.1038/cti.2017.18

Altered regulatory T-cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

Clin Transl Immunology. 2017 May 26;6(5):e143. doi: 10.1038/cti.2017.18. eCollection 2017 May.

Authors

Anderson P Jones¹, Stephanie Trend¹, Scott N Byrne^{2

3}, Marzena J Fabis-Pedrini⁴, Sian Geldenhuys¹, David Nolan^{5

6}, David R Booth³, William M Carroll⁴, Robyn M Lucas⁷, Allan G Kermode^{4

5}, Prue H Hart¹

Affiliations

¹ Telethon Kids Institute, University of Western Australia, West Perth, Western Australia, Australia.
² Cellular Photoimmunology Group, Infectious Diseases & Immunology, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
³ Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
⁴ Centre for Neuromuscular and Neurological Disorders, Western Australian Neuroscience Research Institute, University of Western Australia, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
⁵ Institute for Immunology and Infectious Disease, Murdoch University, Perth, Western Australia, Australia.
⁶ Immunology Department, Royal Perth Hospital, Perth, Western Australia, Australia.
⁷ National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Canberra, Australian Capital Territory, Australia.

Abstract

Development of multiple sclerosis (MS) is frequently preceded by an acute or subacute neurological disturbance referred to as clinically isolated syndrome (CIS). The specific immunological disturbances present in CIS remain underexamined. This study analysed peripheral blood mononuclear cells from n=18 treatment-naive individuals with recently diagnosed CIS (<120 days) for disturbances in the phenotype of T regulatory (Treg), follicular T regulatory (Tfr), T helper (Th), follicular T helper (Tfh) and B cells. Relative to healthy controls (n=19), CIS was associated with lower proportions of suppressive CD45RA⁺FoxP3^lo Treg and Tfr cells and greater proportions of non-suppressive CD45RA^-FoxP3^lo and Th17-like Treg and Tfr. Lower Helios expression (maen fluorescent intensity) was measured across all Treg and Tfr fractions in the CIS group, suggesting less potent regulatory function. Greater frequencies of activated, efficient B-cell helper Tfh subsets and a trend for a higher proportion of IgD^-CD27^- B cells was also detected in the CIS group, characteristics that were positively correlated with Treg and Tfr Helios expression. These results indicate that Treg and Tfr impairment is an early feature in MS.