| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Immunology, National Eye Institute, Islet and Autoimmunity Branch, and Transplantation Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
We examined the role of CD40/CD40L interactions on the development of experimental autoimmune uveoretinitis (EAU), a cell-mediated, Th1-driven autoimmune disease that serves as a model for autoimmune uveitis in humans. EAU-susceptible B10.RIII mice immunized with the retinal autoantigen interphotoreceptor retinoid binding protein in CFA and treated with anti-CD40L Ab (MR1) had reduced incidence and severity of disease. Real-time PCR analysis revealed that the innate and adaptive responses of protected mice were reduced, without an obvious shift toward a Th2 cytokine profile. In contrast to some other reports, no evidence was found for regulatory cells in adoptive transfer experiments. To determine whether CD40L blockade resulted in long-term tolerance, mice protected by treatment with MR1 Ab were rechallenged for uveitis after circulating MR1 Ab levels dropped below the detection limit of ELISA. MR1-treated mice developed severe EAU and strong cellular responses to interphotoreceptor retinoid binding protein, comparable to those of control mice. These responses were higher than in mice that had not received the primary immunization concurrently with anti-CD40L treatment. We conclude that 1) CD40/CD40L interaction is required for EAU and its disruption prevents disease development; 2) CD40L blockade inhibits the innate response to immunization and reduces priming, but does not result in immune deviation; and 3) protection is dependent on persistence of anti-CD40L Abs, and long-term tolerance is not induced. Furthermore, immunological memory develops under cover of CD40L blockade causing enhanced responses upon rechallenge. Taken together, our data suggest that ongoing CD40/CD40L blockade might be required to maintain a therapeutic effect against uveitis.
This article has been cited by other articles:
|
|
 |
|
  V. W.S. Lee, X. Qin, Y. Wang, G. Zheng, Y. Wang, Y. Wang, J. Ince, T. K. Tan, L. K. Kairaitis, S. I. Alexander, et al. The CD40-CD154 co-stimulation pathway mediates innate immune injury in adriamycin nephrosis Nephrol. Dial. Transplant., November 4, 2009; (2009) gfp569v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-F. Gong, L.-X. Xiang, and J.-Z. Shao CD154-CD40 Interactions Are Essential for Thymus-Dependent Antibody Production in Zebrafish: Insights into the Origin of Costimulatory Pathway in Helper T Cell-Regulated Adaptive Immunity in Early Vertebrates J. Immunol., June 15, 2009; 182(12): 7749 - 7762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-A. C. Portillo, J. Van Grol, L. Zheng, G. Okenka, K. Gentil, A. Garland, E. C. Carlson, T. S. Kern, and C. S. Subauste CD40 Mediates Retinal Inflammation and Neurovascular Degeneration J. Immunol., December 15, 2008; 181(12): 8719 - 8726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Agarwal, R. Horai, A. M. Viley, P. B. Silver, R. S. Grajewski, S. Bo Su, A. T. Yazdani, W. Zhu, M. Kronenberg, P. J. Murray, et al. Abrogation of Anti-Retinal Autoimmunity in IL-10 Transgenic Mice Due to Reduced T Cell Priming and Inhibition of Disease Effector Mechanisms J. Immunol., April 15, 2008; 180(8): 5423 - 5429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kitamei, K. Iwabuchi, K. Namba, K. Yoshida, Y. Yanagawa, N. Kitaichi, M. Kitamura, S. Ohno, and K. Onoe Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-{kappa}B (NF-{kappa}B), pyrrolidine dithiocarbamate J. Leukoc. Biol., June 1, 2006; 79(6): 1193 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Okamoto Effect of rituximab in refractory SLE: inhibition of Th1? Rheumatology, January 1, 2006; 45(1): 121 - 122. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
