Blockade of costimulation through B7/CD28 inhibits experimental autoimmune uveoretinitis, but does not induce long-term tolerance.
It has been reported that costimulation blockade can result in T cell anergy. We investigated the effects of blocking costimulatory molecules in vivo on the development of experimental autoimmune uveoretinitis (EAU), a model for autoimmune uveitis in humans that is induced in mice by immunization with the retinal Ag interphotoreceptor retinoid binding protein. B10.A mice immunized with a uveitogenic regimen of interphotoreceptor retinoid-binding protein were treated with Abs to B7.1 and B7.2 for 2 wk. Evaluation of EAU and immunological responses 1 wk later showed that disease had been abrogated, and cellular responses were suppressed. To determine whether the costimulation blockade resulted in tolerance, adult-thymectomized mice immunized for uveitis and treated with anti-B7 or anti-CD28 were rechallenged for uveitis induction 5 wk after the initial immunization. Although confirmed to be disease free after the initial immunization, both anti-B7- and anti-CD28-treated mice developed severe EAU and elevated cellular responses after the rechallenge, equivalent to those of control mice. We conclude that in this model costimulatory blockade in vivo prevents the development of autoimmune disease, but does not result in long-term tolerance. The data are compatible with the interpretation that B7/CD28 blockade prevents generation of effector, but not of memory, T cells.
Silver
P B
PB
Laboratory of Immunology and Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, and Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hathcock
K S
KS
Chan
C C
CC
Wiggert
B
B
Caspi
R R
RR
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000276:immunology* / Q000502:physiology; D018122:B7-1 Antigen / Q000276:immunology* / Q000502:physiology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D005136:Eye Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D012173:Retinitis / Q000276:immunology* / Q000517:prevention & control*; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000276:immunology* / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C497965:Cd86 protein, mouse