The level of thymic expression of RPE65 inversely correlates with its capacity to induce experimental autoimmune uveitis (EAU) in different rodent strains.
We have previously shown that immunization with RPE65 produces in rats of four strains a severe inflammatory eye disease, designated experimental autoimmune uveitis (EAU). Here, we examined the uveitogenicity of RPE65 in six strains of mice. Only one strain, C57Bl/6, was found to develop consistently moderate levels of EAU, whereas other strains (BALB/c, B10.A, B10.BR, B10.RIII, C57BL/10J) were found to be essentially resistant to disease induced by RPE65. Analysis of the expression of RPE65 mRNA in thymi of the six mouse strains revealed detectable levels of the transcript in all strains, but with remarkable quantitative differences, with the lowest levels seen in thymi of C57Bl/6 mice, the only strain susceptible to RPE65-induced EAU. Moreover, unlike the finding with the mice, no RPE65 mRNA was detected in thymi of any of the four rat strains (Lewis, BN, F344, SHR) all of which are susceptible to the disease. These data thus indicate that the susceptibility to RPE65-induced EAU is inversely related to the thymic expression of the molecule. The data also suggest that this disease can be induced only in mice in which thymic expression of RPE65 is sufficiently low to allow the escape from deletion of T-cells with the adequate capacity to initiate the pathogenic immune response.
Ham
Don-Il
DI
Laboratory of Immunology, National Eye Institute, National Institute of Health, Bethesda, MD 20892-1857, USA.
Fujimoto
Chiaki
C
Gentleman
Susan
S
Chan
Chi-Chao
CC
Yu
Cheng-Rong
CR
Yu
Shirley
S
Egwuagu
Charles E
CE
Michael Redmond
T
T
Gery
Igal
I
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins; D004198:Disease Susceptibility; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000633:toxicity; D005260:Female; D015870:Gene Expression; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013045:Species Specificity; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism*; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D005136:Eye Proteins; D012333:RNA, Messenger; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase