CCR5-deficient mice develop experimental autoimmune uveoretinitis in the context of a deviant effector response.
OBJECTIVE
Experimental autoimmune uveoretinitis (EAU) is an organ-specific, Th1-cell-mediated disease that targets the neural retina. CCR5 is a chemokine receptor expressed on Th1 cells that promotes their migration. In CCR5-deficient mice, we examined the role of CCR5 in the development of EAU induced by immunization with interphotoreceptor retinoid-binding protein (IRBP) peptide.


METHODS
Wild-type or CCR5-deficient B6 mice were immunized with human IRBP peptide 1-20 (hIRBP-p), and the severity of EAU was assessed clinically and histologically. Splenocytes and cells of regional lymph nodes near the eye were collected and their proliferation and production of IL-6, IL-10, IFN-gamma, and CCL2 (MCP-1) in response to hIRBP-p stimulation were measured. Moreover, the intraocular levels of these cytokines were analyzed.


RESULTS
Immunization with hIRBP-p induced EAU in CCR5-deficient mice with a severity comparable to that in wild-type mice. Histologically, T-cell infiltration of the eye was reduced, but granulocyte infiltration was augmented in CCR5-deficient mice. Although splenic T cells from CCR5-deficient mice produced IFN-gamma but not IL-10 on stimulation by hIRBP-p, T cells from the regional lymph nodes failed to produce both cytokines. IL-6 production in the eye and IL-6 and CCL2 production by splenic T cells were predominantly augmented in CCR5-deficient mice.


CONCLUSIONS
The development of EAU is not prevented in CCR5-deficient mice. Although T-cell infiltration into the eye is apparently reduced in CCR5-deficient mice, the defect is compensated for by granulocyte infiltration, supposedly mediated by augmented intraocular production of IL-6.
Takeuchi
Aya
A
Department of Ophthalmology, Tokyo Medical University, Japan.
Usui
Yoshihiko
Y
Takeuchi
Masaru
M
Hattori
Takaaki
T
Kezuka
Takeshi
T
Suzuki
Jun
J
Okunuki
Yoko
Y
Iwasaki
Takuya
T
Haino
Makoto
M
Matsushima
Kouji
K
Usui
Masahiko
M
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000633:toxicity; D005260:Female; D007114:Immunization; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D019713:Receptors, CCR5 / Q000502:physiology*; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000633:toxicity; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D016207:Cytokines; D005136:Eye Proteins; D019713:Receptors, CCR5; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial