Regulatory T cells exhibit enhanced migratory characteristics, a feature impaired in patients with multiple sclerosis.
Migration of immune cells characterizes inflammation and plays a key role in autoimmune diseases such as MS. CD4(+)Foxp3(+) regulatory T cells (Treg) have the potential to dampen immune responses but show functional impairment in patients with MS. We here show that murine Treg exhibit higher constitutive cell motility in horizontal migration on laminin, surpass non-Treg in transwell assays through microporous membranes as well as across primary brain endothelium and are present in the naïve CNS to a significantly higher extent compared to spleen, lymph nodes and blood. Likewise, human Treg from healthy donors significantly exceed non-Treg in migratory rates across primary human brain endothelium. Finally, we investigated whether the propensity to migrate is impaired as a feature of autoimmunity and therefore tested patients with MS. Treg from patients with stable relapsing-remitting MS show significantly impaired migratory capacity under non-inflammatory conditions compared to healthy donors. We hypothesize that the enhanced propensity to migrate is a feature of Treg that allows for an equilibrium in parenchymal immune surveillance, e.g. of the CNS. Impaired Treg migration across the intact blood-brain barrier, as observed for Treg from patients with MS, indicates a broader functional deficiency hypothetically contributing to early CNS lesion development or phases of MS remissions.
Department of Neurology, Inflammatory Disorders of the Nervous System and Neurooncology, University of Muenster, Muenster, Germany.
Tilman
T
Schneider-Hohendorf
Max-Philipp
MP
Stenner
Christian
C
Weidenfeller
Alla L
AL
Zozulya
Ole J
OJ
Simon
Nicholas
N
Schwab
Heinz
H
Wiendl
D000328:Adult; D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000473:pathology*; D015704:CD4 Antigens / Q000096:biosynthesis; D054441:Cell Migration Assays, Leukocyte; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors