Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity
AuthorsGrajewski, Rafael S.
Silver, Phyllis B.
Agarwal, Rajeev K.
Liou, Gregory I.
Caspi, Rachel R.
MetadataShow full item record
AbstractSusceptibility to experimental autoimmune uveitis (EAU), a model for human uveitis induced in mice with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP), is controlled by â naturalâ CD4+CD25+ regulatory T (T reg) cells. To examine whether endogenous expression of IRBP is necessary to generate these T reg cells, we studied responses of IRBP knockout (KO) versus wild-type (WT) mice. Unexpectedly, not only WT but also IRBP KO mice immunized with a uveitogenic regimen of IRBP in complete Freund's adjuvant (CFA) exhibited CD25+ regulatory cells that could be depleted by PC61 treatment, which suppressed development of uveitogenic effector T cells and decreased immunological responses to IRBP. These EAU-relevant T reg cells were not IRBP specific, as their activity was not present in IRBP KO mice immunized with IRBP in incomplete Freund's adjuvant (IFA), lacking mycobacteria (whereas the same mice exhibited normal T reg cell activity to retinal arrestin in IFA). We propose that mycobacterial components in CFA activate T reg cells of other specificities to inhibit generation of IRBP-specific effector T cells in a bystander fashion, indicating that effective T reg cells can be antigen nonspecific. Our data also provide the first evidence that generation of specific T reg cells to a native autoantigen in a mouse with a diverse T cell repertoire requires a cognate interaction.
CitationJ Exp Med. 2006 Apr 17; 203(4):851-856
- Hydrodynamic vaccination with DNA encoding an immunologically privileged retinal antigen protects from autoimmunity through induction of regulatory T cells.
- Authors: Silver PB, Agarwal RK, Su SB, Suffia I, Grajewski RS, Luger D, Chan CC, Mahdi RM, Nickerson JM, Caspi RR
- Issue date: 2007 Oct 15
- Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis.
- Authors: Keino H, Takeuchi M, Usui Y, Hattori T, Yamakawa N, Kezuka T, Sakai JI, Usui M
- Issue date: 2007 Jan
- Blockade of interleukin-6 signaling suppresses not only th17 but also interphotoreceptor retinoid binding protein-specific Th1 by promoting regulatory T cells in experimental autoimmune uveoretinitis.
- Authors: Haruta H, Ohguro N, Fujimoto M, Hohki S, Terabe F, Serada S, Nomura S, Nishida K, Kishimoto T, Naka T
- Issue date: 2011 May 17
- Ex-vivo tolerogenic F4/80⁺ antigen-presenting cells (APC) induce efferent CD8⁺ regulatory T cell-dependent suppression of experimental autoimmune uveitis.
- Authors: Hsu SM, Mathew R, Taylor AW, Stein-Streilein J
- Issue date: 2014 Apr
- Breakdown of immune privilege and spontaneous autoimmunity in mice expressing a transgenic T cell receptor specific for a retinal autoantigen.
- Authors: Horai R, Silver PB, Chen J, Agarwal RK, Chong WP, Jittayasothorn Y, Mattapallil MJ, Nguyen S, Natarajan K, Villasmil R, Wang P, Karabekian Z, Lytton SD, Chan CC, Caspi RR
- Issue date: 2013 Aug