In:
The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 9 ( 2009-05-01), p. 5331-5341
Kurzfassung:
Cytokine-Ag fusion proteins represent a novel approach for induction of Ag-specific tolerance and may constitute an efficient therapy for autoimmune disease. This study addressed whether a fusion protein containing rat IFN-β and the encephalitogenic 73–87 determinant of myelin basic protein (i.e., the neuroantigen, or NAg) could prevent or treat experimental autoimmune encephalomyelitis (EAE) in Lewis rats. The optimal structure of the fusion protein was comprised of the rat IFN-β cytokine as the N-terminal domain with an enterokinase (EK) linker to the NAg domain. Both cytokine and NAg domains had full biological activity. Subcutaneous administration of 1 nmol of IFNβ-NAg fusion protein in saline on days −21, −14, and −7 before encephalitogenic challenge on day 0 resulted in a substantial attenuation of EAE. In contrast, administration of IFN-β or NAg alone did not affect susceptibility to EAE. The covalent attachment of IFN-β and NAg was not necessary, because separate injections of IFN-β and NAg at adjacent sites were as effective as injection of IFNβ-NAg for prevention of disease. When treatment was initiated after disease onset, the rank order of inhibitory activity was as follows: the IFNβ-NAg fusion protein ≥ a mixture of IFN-β plus NAg & gt; IFN-β & gt; NAg. The novel finding that IFN-β acts as a tolerogenic adjuvant as well as a tolerogenic fusion partner may have significance for development of tolerogenic vaccines.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.0803756
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2009
ZDB Id:
1475085-5
