TY - JOUR
T1 - Anti-CD137 mAb treatment inhibits experimental autoimmune uveitis by limiting expansion and increasing apoptotic death of uveitogenic T cells
AU - Shao, Hui
AU - Fu, Yangxin
AU - Liao, Tianjiang
AU - Peng, Young
AU - Chen, Lieping
AU - Kaplan, Henry J.
AU - Sun, Deming
PY - 2005/2
Y1 - 2005/2
N2 - PURPOSE. To explore the role of CD137 in the pathogenesis of experimental autoimmune uveitis (EAU) and to compare the inhibitory mechanism of anti-CD 137 mAb with other costimulatory blockers. METHODS. EAU was induced in B10RIII mice, either by immunization with a uveitogenic peptide, IRBP161-180, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of IRBP16l-180-speciflc T cells. The effect of an agonistic anti-CD137 mAb (2A) on the in vivo induction of disease was studied. Subsequently, the mechanism by which anti-CD137 mAb inhibits uveitogenic T-cell activation was investigated, by using the adoptive transfer of T cells derived from anti-CD137 mAb-treated mice, and in vitro, using the proliferative response and apoptotic cell death of IRBP-speciflc T cells from anti-CD137 mAb-treated mice. RESULTS. Administration of anti-CD137 mAb prevented the development of de novo induced uveitis, but not that induced by adoptive transfer of pathogenic T cells. Furthermore, anti-CD137 mAb treatment of the animals resulted in decreased expansion of uveitogenic T cells, accompanied by increased activated cell death and resistance to reinduction of uveitis. CONCLUSIONS. CD137 plays a critical role in the induction, rather than the effector, phase of the disease. Different costimulatory molecules have different effects on the activation of autoreactive T cells by acting in different phases of T-cell activation.
AB - PURPOSE. To explore the role of CD137 in the pathogenesis of experimental autoimmune uveitis (EAU) and to compare the inhibitory mechanism of anti-CD 137 mAb with other costimulatory blockers. METHODS. EAU was induced in B10RIII mice, either by immunization with a uveitogenic peptide, IRBP161-180, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of IRBP16l-180-speciflc T cells. The effect of an agonistic anti-CD137 mAb (2A) on the in vivo induction of disease was studied. Subsequently, the mechanism by which anti-CD137 mAb inhibits uveitogenic T-cell activation was investigated, by using the adoptive transfer of T cells derived from anti-CD137 mAb-treated mice, and in vitro, using the proliferative response and apoptotic cell death of IRBP-speciflc T cells from anti-CD137 mAb-treated mice. RESULTS. Administration of anti-CD137 mAb prevented the development of de novo induced uveitis, but not that induced by adoptive transfer of pathogenic T cells. Furthermore, anti-CD137 mAb treatment of the animals resulted in decreased expansion of uveitogenic T cells, accompanied by increased activated cell death and resistance to reinduction of uveitis. CONCLUSIONS. CD137 plays a critical role in the induction, rather than the effector, phase of the disease. Different costimulatory molecules have different effects on the activation of autoreactive T cells by acting in different phases of T-cell activation.
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U2 - 10.1167/iovs.04-0835
DO - 10.1167/iovs.04-0835
M3 - Article
C2 - 15671287
AN - SCOPUS:13944278756
SN - 0146-0404
VL - 46
SP - 596
EP - 603
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 2
ER -