Abstract
Purpose: :
Previously we developed and characterized a T cell receptor (TCR) transgenic (Tg) B10.A mouse (bgalTCR) specific for b-galactosidase (bgal) to study the immune response to bgal when expressed as a retinal neo-self antigen (Ag). Using these mice we observed mechanisms of immune regulation induced by retinal Ags that were different than those reported using the 3A9 TCR Tg T cell/retinal hen egg lysozyme Ag system (McPherson, et al., J. Immunol. 182; Ham, et al., IOVS. 45; and Lambe, et al., J. Immunol. 178). In order to confirm the validity of our model we examined the immune response to retinal bgal using a different TCR Tg mouse. Here we report on a B6 TCR-Tg mouse specific for bgal; BG2.
Methods: :
A TCR Tg mouse on the B6 MHC background specific for a class II MHC restricted (CD4+ T cell) epitope of bgal was developed. Identification of the BG2 T cell epitope was done by in vitro proliferation and cytokine assays using overlapping peptides of bgal. Pathogenicity of the epitope was assayed in adaptive transfer of peptide-stimulated BG2 T cells. The regulatory T cell (Treg) immune regulation induced by retinal expression of bgal was analyzed by comparing the DTH (ear swelling) response of BG2 mice to B6arrbgal (Tg photoreceptor cell bgal expression) x BG2 double Tg mice.
Results: :
Two peptides of bgal containing the common epitope of SVTLPAASHAI induced proliferation and production of IL-2, IFNg, and TNFa by BG2 T cells. Adoptive transfer of BG2 T cells stimulated with either peptide induced experimental autoimmune uveoretinitis (EAU) in B6arrbgal mice. B6arrbgal x BG2 double Tg mice exhibited reduced ear swelling compared to BG2 mice indicative of bgal-specific regulatory immune response associated with its expression in photoreceptor cells. All of these results are similar to those obtained using bgalTCR mice.
Conclusions: :
We have developed and characterized the immune response of a B6 TCR Tg mouse specific for a retinal neo-self antigen. The fact that we obtained similar results with both our B10.A and B6 TCR Tg mice supports our findings that photoreceptor cell Ags induce a Treg mediated immune regulation.
Keywords: immunomodulation/immunoregulation • immune tolerance/privilege • autoimmune disease