Fatigue is not associated with impaired function of regulatory T cells in untreated patients with multiple sclerosis.
BACKGROUND
The pathophysiology of multiple sclerosis (MS)-associated fatigue is poorly understood. Immunological mechanisms may play a role. Alterations in immunological profile indicate a chronic immune activation in MS patients with fatigue. T-regulatory (Treg) cells seem to play a key role in coordinating autoimmune mechanisms in MS. This is the first study investigating the relationship between Treg cell function and fatigue in MS patients.


METHODS
In this cross-sectional in vitro, ex vivo study, we isolated peripheral blood mononuclear cells (PBMCs) from 20 MS patients with fatigue, determined lymphocyte subsets by flow cytometry and suppressive function of Treg cells in PBMC cultures with antigen stimulation. Forkhead box protein 3 expression was evaluated by PCR. Results were compared with 20 MS patients without fatigue and with 19 healthy controls.


RESULTS
Leukocytes and lymphocyte subsets including Treg cell frequency did not differ in patients with and without fatigue. Co-culturing of Treg cells with CD4+CD25- cells did not lead to a significant suppression of myelin basic protein- and pokeweed mitogen-induced proliferation in MS patients in contrast to healthy controls. There were no statistical differences between MS patients with and without fatigue regarding this suppression activity.


CONCLUSIONS
Fatigue seems not to be associated with impaired function of Treg cells in untreated MS patients.
Yaldizli
Ozguer
O
Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland. yaldizli@gmx.net
Kumar
Manoj
M
Vago
Susanne
S
Kreuzfelder
Erich
E
Limmroth
Volker
V
Putzki
Norman
N
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D005221:Fatigue / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D051858:Forkhead Transcription Factors; D012333:RNA, Messenger