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

Hdl Handle:
http://hdl.handle.net/10675.2/544
Title:
Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity
Authors:
Grajewski, Rafael S.; Silver, Phyllis B.; Agarwal, Rajeev K.; Su, Shao-Bo; Chan, Chi-Chao ( 0000-0001-9460-8049 ) ; Liou, Gregory I.; Caspi, Rachel R. ( 0000-0002-7140-7671 )
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 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.
Citation:
J Exp Med. 2006 Apr 17; 203(4):851-856
Issue Date:
17-Apr-2006
URI:
http://hdl.handle.net/10675.2/544
DOI:
10.1084/jem.20050429
PubMed ID:
16585264
PubMed Central ID:
PMC2118294
Type:
Article
ISSN:
1540-9538
Appears in Collections:
Department of Ophthalmology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorGrajewski, Rafael S.en_US
dc.contributor.authorSilver, Phyllis B.en_US
dc.contributor.authorAgarwal, Rajeev K.en_US
dc.contributor.authorSu, Shao-Boen_US
dc.contributor.authorChan, Chi-Chaoen_US
dc.contributor.authorLiou, Gregory I.en_US
dc.contributor.authorCaspi, Rachel R.en_US
dc.date.accessioned2012-10-26T16:26:36Z-
dc.date.available2012-10-26T16:26:36Z-
dc.date.issued2006-04-17en_US
dc.identifier.citationJ Exp Med. 2006 Apr 17; 203(4):851-856en_US
dc.identifier.issn1540-9538en_US
dc.identifier.pmid16585264en_US
dc.identifier.doi10.1084/jem.20050429en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/544-
dc.description.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.en_US
dc.rightsCopyright © 2006, The Rockefeller University Pressen_US
dc.subjectBrief Definitive Reportsen_US
dc.subjectBrief Definitive Reporten_US
dc.titleEndogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunityen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2118294en_US
dc.contributor.corporatenameDepartment of Ophthalmology-

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