Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity

Rafael S. Grajewski, Phyllis B. Silver, Rajeev K. Agarwal, Shao Bo Su, Chi Chao Chan, Gregory I Liou, Rachel R. Caspi

Research output: Contribution to journalArticle

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Abstract

Susceptibility 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 "natural" 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.

Original languageEnglish (US)
Pages (from-to)851-856
Number of pages6
JournalJournal of Experimental Medicine
Volume203
Issue number4
DOIs
StatePublished - Apr 17 2006

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Regulatory T-Lymphocytes
Autoimmunity
Uveitis
Freund's Adjuvant
T-Lymphocytes
Knockout Mice
interstitial retinol-binding protein
Arrestin
Antigens
Autoantigens
Mycobacterium

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity. / Grajewski, Rafael S.; Silver, Phyllis B.; Agarwal, Rajeev K.; Su, Shao Bo; Chan, Chi Chao; Liou, Gregory I; Caspi, Rachel R.

In: Journal of Experimental Medicine, Vol. 203, No. 4, 17.04.2006, p. 851-856.

Research output: Contribution to journalArticle

Grajewski, Rafael S. ; Silver, Phyllis B. ; Agarwal, Rajeev K. ; Su, Shao Bo ; Chan, Chi Chao ; Liou, Gregory I ; Caspi, Rachel R. / Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity. In: Journal of Experimental Medicine. 2006 ; Vol. 203, No. 4. pp. 851-856.
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