TY - JOUR
T1 - Lymphotoxin β receptor-lg fusion protein treatment blocks actively induced, but not adoptively transferred, uveitis in Lewis rats
AU - Shao, Hui
AU - Fu, Yangxin
AU - Song, Lei
AU - Sun, Sheler
AU - Kaplan, Herry J.
AU - Sun, Deming
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Previous studies have shown that treatment of rodents with a lymphotoxin (LT)-β receptor-Ig fusion protein (LTβR-Ig), which binds to both LT and LIGHT, prevents the development of autoimmune diseases, but the mechanism involved is unclear. To explore the potential role of LT or LIGHT in the pathogenesis of autoimmune uveitis, uveitis was induced in Lewis rats either by immunization with an uveitogenic peptide, R16, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of R16-specific T cells. Interestingly, LTβR-Ig treatment completely prevented actively induced uveitis, but not the adoptively transferred disease. We also show that LTβR-Ig-treated R16-injected rats had a significantly decreased T cell response to R16 and that herpesvirus entry mediator (HVEM)-Ig, a fusion protein that blocks LIGHT, also inhibited disease development. Our results suggest that LT or LIGHT plays a critical role in the induction, rather than the effector, phase of the disease.
AB - Previous studies have shown that treatment of rodents with a lymphotoxin (LT)-β receptor-Ig fusion protein (LTβR-Ig), which binds to both LT and LIGHT, prevents the development of autoimmune diseases, but the mechanism involved is unclear. To explore the potential role of LT or LIGHT in the pathogenesis of autoimmune uveitis, uveitis was induced in Lewis rats either by immunization with an uveitogenic peptide, R16, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of R16-specific T cells. Interestingly, LTβR-Ig treatment completely prevented actively induced uveitis, but not the adoptively transferred disease. We also show that LTβR-Ig-treated R16-injected rats had a significantly decreased T cell response to R16 and that herpesvirus entry mediator (HVEM)-Ig, a fusion protein that blocks LIGHT, also inhibited disease development. Our results suggest that LT or LIGHT plays a critical role in the induction, rather than the effector, phase of the disease.
KW - Autoimmunity
KW - Costimulation
KW - Interphotoreceptor retinoid-binding protein
KW - Lymphotoxin β receptor-lg fusion protein
KW - Uveitis
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U2 - 10.1002/eji.200323745
DO - 10.1002/eji.200323745
M3 - Article
C2 - 12778492
AN - SCOPUS:0038420931
SN - 0014-2980
VL - 33
SP - 1736
EP - 1743
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 6
ER -