Reactivation of uveitogenic T cells by retinal astrocytes derived from experimental autoimmune uveitis-prone B10RIII mice.
OBJECTIVE
To determine the involvement of retinal astrocytes (RACs) in T cell-mediated experimental autoimmune uveitis (EAU).


METHODS
Frozen sections of eyes from naive mice or mice with EAU were stained for glial fibrillary acidic protein (GFAP) or major histocompatibility complex (MHC) class II molecules and were examined by confocal microscopy. RACs were isolated and cocultured with interphotoreceptor retinoid-binding protein (IRBP) peptide-specific T cells. The proliferation and cytokine production of responder T cells were determined by [(3)H]-thymidine incorporation and ELISA, respectively.


RESULTS
The development of intraocular inflammation was associated with increased GFAP-positive cells in the retina. RACs from EAU-prone mice (B10RIII) activated uveitogenic T cells in vitro, enhanced T-cell proliferation and the production of proinflammatory cytokines, and increased the numbers of IL-17(+) IRBP T cells in the inflamed eye. The interaction between local RACs and IRBP-specific T cells was regulated by a distinct pattern of costimulatory molecules. In addition, the ability of IRBP-specific T cells to interact with RACs was dependent on whether the latter were derived from EAU-prone (B10RIII) or EAU-low susceptible (C57Bl/6) strains of mice.


CONCLUSIONS
This study suggests that the RACs in EAU-prone mice contribute to the reactivation of pathogenic T cells in the eye, leading to intraocular inflammation and tissue damage.
Jiang
Guomin
G
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, 301 E. Muhammad Ali Boulevard, Louisville, KY 40202, USA.
Ke
Yan
Y
Sun
Deming
D
Han
Gencheng
G
Kaplan
Henry J
HJ
Shao
Hui
H
D019264:Adoptive Transfer; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001327:Autoimmune Diseases / Q000276:immunology*; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000633:toxicity; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C515934:Il17a protein, rat