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S.W. McPherson, N.D. Heuss, D.S. Gregerson; Pathogenicity and Regulation of T Cells Specific for the Retinal Neo–Self Antigen Beta–Galactosidase . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4550.
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© ARVO (1962-2015); The Authors (2016-present)
To analyze the response and regulation of T cells specific for beta–galactosidase (b–gal) in mice that do and do not express b–gal in the retina.
We have previously described the development of transgenic (Tg) mice expressing b–gal specifically in the photoreceptor cells of the retina (hi–arr–b–gal mice, Gregerson, et al. J. Immunol. 163:1073) and the generation of an MHC class II restricted T cell receptor Tg mice specific for b–gal (3E9–Tg, ARVO 2003 abstract #1053). Thymic expression of b–gal was assayed by RT–PCR. The pathogenicity of the 3E9–Tg T cells was analyzed by the induction of experimental autoimmune uveoretinitis (EAU) following adoptive transfer of antigen–activated T cells into hi–arr–b–gal and hi–arr–b–gal/Rag–/– mice. Induction of immune regulation by photoreceptor cell b–gal was assayed by analysis of the delayed–type hypersensitivity (DTH) response following ear testing of 3E9–Tg and 3E9/hi–arr–b–gal double Tg mice with b–gal antigen. The identification of regulatory T cells (Tregs) was assayed by adoptive transfer of candidate hi–arr–b–gal lymphoid cell populations into b–gal negative recipients followed by antigen priming and ear testing.
In vitro antigen–activated, primary 3E9–Tg T cells transferred similar levels of EAU in hi–arr–b–gal and hi–arr–b–gal/Rag–/– recipients. Ear swelling associated with the DTH response to b–gal was significantly reduced in naive 3E9/hi–arr–b–gal mice compared to naive 3E9–Tg mice. RT–PCR analysis of hi–arr–b–gal thymus showed no expression of b–gal. Adoptive transfer studies of candidate Treg populations from lymphoid organs of hi–arr–b–gal mice showed that the Tregs were CD3+CD4+ T cells. Depletion of CD25+ cells resulted in the loss of regulatory activity but magnetic bead–enriched CD25+ populations failed to express regulatory activity after adoptive transfer.
The presence of b–gal in photoreceptor cells down regulates the DTH and pathogenic responses of 3E9 T cells to antigen. The endogenous Tregs appear to be peripherally generated and are distinct from Tregs induced by antigen inoculation of the anterior chamber of the eye or by i.v. inoculation.
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