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IFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis
| Content Provider | Scilit |
|---|---|
| Author | Wang, Duncheng Ghosh, Debjani Islam, S. M. Touhidul Moorman, Cody D. Thomason, Ashton E. Wilkinson, Daniel S. Mannie, Mark D. |
| Copyright Year | 2016 |
| 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 $CD44^{high}$ $CD25^{+}$ 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. |
| Ending Page | 3007 |
| Page Count | 16 |
| Starting Page | 2992 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1500411 |
| Journal | The Journal of Immunology |
| Issue Number | 8 |
| Volume Number | 197 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2016-10-15 |
| Access Restriction | Open |
| Subject Keyword | Regulatory T Cells Interferon-beta Eae/ms |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |