IFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis
Author
Wang, Duncheng; Ghosh, Debjani; Islam, Touhidul; Moorman, Cody; Thomason, Ashton; Wilkinson, Daniel; Mannie, Mark
Abstract
This study introduces a flexible format for tolerogenic vaccination that incorporates IFN-β and neuroantigen (NAg) in the Alum adjuvant. Tolerogenic vaccination required all three components, IFN-β, NAg, and Alum, for inhibition of experimental autoimmune encephalomyelitis (EAE) and induction of tolerance. Vaccination with IFN-β + NAg in Alum ameliorated NAg-specific sensitization and inhibited EAE in C57BL/6 mice in pretreatment and therapeutic regimens. Tolerance induction was specific for the tolerogenic vaccine Ag PLP178-191 or myelin oligodendrocyte glycoprotein (MOG)35–55 in proteolipid protein– and MOG-induced models of EAE, respectively, and was abrogated by pretreatment with a depleting anti-CD25 mAb. IFN-β/Alum–based vaccination exhibited hallmarks of infectious tolerance, because IFN-β + OVA in Alum–specific vaccination inhibited EAE elicited by OVA + MOG in CFA but not EAE elicited by MOG in CFA. IFN-β + NAg in Alum vaccination elicited elevated numbers and percentages of FOXP3+ T cells in blood and secondary lymphoid organs in 2D2 MOG-specific transgenic mice, and repeated boosters facilitated generation of activated CD44high CD25+ regulatory T cell (Treg) populations. IFN-β and MOG35–55 elicited suppressive FOXP3+ Tregs in vitro in the absence of Alum via a mechanism that was neutralized by anti–TGF-β and that resulted in the induction of an effector CD69+ CTLA-4+ IFNAR+ FOXP3+ Treg subset. In vitro IFN-β + MOG–induced Tregs inhibited EAE when transferred into actively challenged recipients. Unlike IFN-β + NAg in Alum vaccines, vaccination with TGF-β + MOG35-55 in Alum did not increase Treg percentages in vivo. Overall, this study indicates that IFN-β + NAg in Alum vaccination elicits NAg-specific, suppressive CD25+ Tregs that inhibit CNS autoimmune disease. Thus, IFN-β has the activity spectrum that drives selective responses of suppressive FOXP3+ Tregs.
Date
2016-10-15
Citation:
APA:
Wang, Duncheng, & Ghosh, Debjani, & Islam, Touhidul, & Moorman, Cody, & Thomason, Ashton, & Wilkinson, Daniel, & Mannie, Mark. (October 2016).
IFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/8301
MLA:
Wang, Duncheng, and Ghosh, Debjani, and Islam, Touhidul, and Moorman, Cody, and Thomason, Ashton, and Wilkinson, Daniel, and Mannie, Mark.
"IFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis". .
. (),
October 2016.
May 10, 2024.
http://hdl.handle.net/10342/8301.
Chicago:
Wang, Duncheng and Ghosh, Debjani and Islam, Touhidul and Moorman, Cody and Thomason, Ashton and Wilkinson, Daniel and Mannie, Mark,
"IFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis," , no.
(October 2016),
http://hdl.handle.net/10342/8301 (accessed
May 10, 2024).
AMA:
Wang, Duncheng, Ghosh, Debjani, Islam, Touhidul, Moorman, Cody, Thomason, Ashton, Wilkinson, Daniel, Mannie, Mark.
IFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis. .
October 2016;
():
.
http://hdl.handle.net/10342/8301. Accessed
May 10, 2024.
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