Interferon beta induces T-helper 2 immune deviation in MS.
OBJECTIVE
To define the in vitro effects of interferon beta la (IFN-beta1a) on myelin basic protein (MBP)-reactive T cells and to determine its regulatory mechanism on cytokine networks in patients with MS.


METHODS
The proliferation and cytokine production of MBP-reactive T-cell clones were measured in thymidine uptake assays and ELISA respectively. The precursor frequency of MBP-reactive T cells was estimated in a microwell culture system.


RESULTS
IFN-beta inhibited the proliferation of established MBP-reactive T-cell clones, which correlated with enhanced production of anti-inflammatory interleukin (IL)-4 and IL-10, and a decrease in tumor necrosis factor alpha (TNF-alpha) and IFN-gamma. When examined with peripheral blood mononuclear cells (PBMCs), IFN-beta was found to reduce the in vitro T-cell responses to MBP, as indicated by the significantly decreased frequency of MBP-reactive T cells. The decreased frequency of MBP-reactive T cells corresponded to an augmented production of IL-4 and IL-10. Although the level of TNF-alpha and IFN-gamma was generally unaltered or decreased, IFN-beta appeared to enhance the production of IFN-gamma in PBMCs derived from some individuals with MS.


CONCLUSIONS
Interferon beta la (IFN-beta) suppresses myelin basic protein (MBP)-reactive T cells and induces immune deviation toward the production of T-helper 2 cytokines, which may contribute to its therapeutic benefit in MS. The study also suggests some heterogeneity in MBP-reactive T-cell responses to IFN-beta in different individuals with MS.
Kozovska
M E
ME
Multiple Sclerosis Research and Neuroimmunology Laboratory, Department of Neurology and Baylor-Methodist International Multiple Sclerosis Center, Houston, TX, USA.
Hong
J
J
Zang
Y C
YC
Li
S
S
Rivera
V M
VM
Killian
J M
JM
Zhang
J Z
JZ
D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004676:Myelin Basic Protein / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D016899:Interferon-beta