Interferon beta-induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells.
BACKGROUND
Naturally occurring regulatory T (T(reg)) cells are functionally impaired in patients with relapsing-remitting multiple sclerosis. We recently showed that prevalences of newly generated CD31-coexpressing naive T(reg) cells (recent thymic emigrant-T(reg) cells) are critical for suppressive function of circulating T(reg) cells, and a shift in the homeostatic composition of T(reg)-cell subsets related to a reduced de novo generation of recent thymic emigrant-T(reg) cells may contribute to the multiple sclerosis (MS)-related T(reg)-cell dysfunction. Interferon beta, an immunomodulatory agent with established efficacy in MS, lowers relapse rates and slows disease progression. Emerging evidence suggests that T(reg)-cell suppressive capacity may increase in patients with MS undergoing treatment with interferon beta, although the mechanisms mediating this effect are uncertain.


OBJECTIVE
To evaluate the effect of interferon beta treatment on the suppressive activity and the homeostasis of circulating T(reg) cells in patients with MS.


METHODS
Twenty patients with relapsing-remitting MS and 18 healthy control subjects.


METHODS
Administration of interferon beta.


METHODS
Effect of interferon beta on T(reg)-cell homeostasis and suppressive capacity.


RESULTS
Suppressive capacities of T(reg) cells were consistently upregulated at 3 and 6 months after treatment with interferon beta. The restoration of T(reg)-cell function was paralleled by increased naive recent thymic emigrant-T(reg) cells and a coincidental reduction in memory T(reg) cells.


CONCLUSIONS
The increase in T(reg)-cell inhibitory capacity mediated by interferon beta treatment can be explained by its effect on the homeostatic balance within the T(reg) cell compartment.
Korporal
Mirjam
M
Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Haas
Juergen
J
Balint
Bettina
B
Fritzsching
Benedikt
B
Schwarz
Alexander
A
Moeller
Sigrid
S
Fritz
Brigitte
B
Suri-Payer
Elisabeth
E
Wildemann
Brigitte
B
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007156:Immunologic Memory / Q000187:drug effects; D016899:Interferon-beta / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D013950:Thymus Gland / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
D007155:Immunologic Factors; D016899:Interferon-beta