Experimental Immunology Section
Research
The research carried out by the Section addresses the following scientific issues:
1) Mechanisms, cells and molecules that participate in the induction or modulation of ocular inflammation. We are using the following animal models for ocular inflammation: (i) experimental autoimmune uveitis (EAU), that is actively induced in mice and rats by immunization with retinal antigens, mostly IRBP or S-antigen, or uveitogenic peptides from their sequence; (ii) ocular inflammation that is induced in transgenic mice expressing hen egg lysozyme (HEL) in their eyes, by adoptively transferring Th1 or Th2 cells specific against HEL. The scientific issues currently being addressed include: (i) analysis of the mechanisms whereby microbial products trigger pathogenic autoimmunity; (ii) participation of antigen-nonspecific lymphocytes in the process of immune-mediated inflammation; (iii) the capacity of natural killer T-cells to modulate immune-mediated ocular inflammation; (iv) modulation of immune-mediated inflammation by synthetically made copolymers, such as Copaxone.
2) Involvement of immune-related molecules in the pathogenic processes of chronic eye diseases such as age-related macular degeneration (AMD). Recently accumulated data indicate that inflammatory processes participate in the pathogenesis of diseases such as AMD or diabetic retinopathy. Animal models for these diseases are not available yet and we are using pathological conditions in animals that resemble the human diseases, namely, light damage, retinal degeneration due to genetic defects and apoptosis due to glutamate toxicity. Eyes of mice undergoing these pathological changes are being examined for deposition of complement and for changes in expression of cytokines, chemokines and molecules that suppress cytokine production, such as GC-BP.
Staff
| Name | Title | |
Igal Gery, Ph.D. |
Section Head | geryi@nei.nih.gov |
| Barbara P. Vistica, M.S | Microbiologist | visticab@nei.nih.gov |
| Hongen Yin, M.D., Ph.D. | Visiting Fellow | yinho@nei.nih.gov |
| Guangpu Shi, M.D. | Research fellow | shig@nei.nih.gov |
| Catherine Cox, B.A. | HHMI-NIH Scholar | coxca@mail.nih.gov |
| Vanessa Montalvo, B.A. | Graduate Student | montalvov@nei.nih.gov |
Recent Publications
Zhang, M., Chan, C.-C., Vistica, B., Hung, V., Wiggert, B., and Gery, I.: Copolymer 1 inhibits experimental autoimmune uveoretinitis. J. Neuroimmunol. 103:189-194, 2000. PubMed
Kozhich, A.T., Chan, C.-C., Gery, I., and Whitcup, S.M.: Recurrent intraocular inflammation in endotoxin-induced uveitis. Invest. Ophthalmol. Vis. Sci. 41:1823-1826, 2000. PubMed
de Vos, A.F., Fukushima, A., Lobanoff, M.C., Vistica, B.P., Lai, J.C., Grivel, J.-C., Wawrousek, E.F., Whitcup, S.M., and Gery, I. Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen. J. Immunol. 164:4594-4600, 2000. PubMed
Gelderman, M.P., Gonzalez-Fernandez, F., Baer, C.A., Wiggert, B., Chan, C.-C., Vistica, B.P., and Gery, I.: Xenopus IRBP, a phylogenetically remote protein, is uveitogenic in Lewis rats. Exp. Eye Res. 70:731-736, 2000. PubMed
Zhang, M., Hung, V., and Gery, I.: Vasoactive intestinal peptide (VIP) exacerbates endotoxin-induced uveitis (EIU) in mice. Curr. Eye Res. 21:913-917, 2000 PubMed
Zhang, M., Fukushima, A., Vistica, B.P., Kim, S.J., Hung, L., Wawrousek, E.F., Egwuagu, C.E., Lee, R.S., Whitcup, S.M., and Gery, I.: Skewed abrogation of tolerance to a neo self-antigen in double-transgenic mice coexpressing the antigen with interleukin-1b or interferon-g. Cell. Immunol. 207:6-12, 2001. PubMed
Tamm, S.A., Whitcup, S.M., Gery, I., Wiggert, B., Nussenblatt, R.B., and Kaiser-Kupfer, M.I.: Immune response to retinal antigens in patients with gyrate atrophy and other hereditary retinal dystrophies. Ocul. Immunol. Inflam. 9:75-84, 2001. PubMed
Kim, S.J., Zhang, M., Vistica, B.P., Chan, C.-C., Shen, D.-F., Wawrousek, E.F., and Gery, I.: Induction of ocular inflammation by T-helper lymphocytes type 2. Invest. Ophthalmol. Vis. Sci., 43: 758-765, 2002. PubMed
Foxman, E.F., Zhang, M., Hurst, S.D., Muchamuel, T., Shen, D., Wawrousek, E.F., Chan, C.-C., and Gery, I.: Inflammatory mediators in uveitis: Differential induction of cytokines and chemokines in Th1 vs. Th2-mediated ocular inflammation. J. Immunol. 168:2483-2492, 2002. PubMed
Gery, I., Nussenblatt, R.B., Chan, C.-C., and Caspi, R.R. Autoimmune diseases of the eye. In: The Molecular Pathology of Autoimmune Diseases, Second Edition, Theofilopoulos A.N., and Bona, C.A., Eds. Taylor & Francis, New York, NY, pp. 978-998, 2002.
Gery, I. and Egwuagu, C.E.: Central tolerance mechanisms in control of susceptibility to autoimmune uveitic disease. Int. Rev. Immunol., 21:89-100, 2002. PubMed
Egwuagu, C.E., Yu, C.-R., Zhang, M., Mahdi, R.M., Kim, S.J., and Gery, I.: Suppressors of cytokine signaling proteins are differentially expressed in Th1 and Th2 cells: Implications for Th cell lineage commitment and maintenance. J. Immunol., 168:3181-3187, 2002. PubMed
Ham, D.-I., Gentleman, S., Chan, C.-C., McDowell, J.H., Redmond, T.M., and Gery, I: RPE65 is highly uveitogenic in rats. Invest. Ophthalmol. Vis. Sci., 43:2258-2263, 2002. PubMed
Zhang, M., Vacchio, M.S., Vistica, B.P., Lesage, S., Egwuagu, C.E., Yu, C.-R., Gelderman, M.P., Kennedy, M.C., Wawrousek, E.F., and Gery, I.: T cell tolerance to a neo-self antigen expressed by thymic epithelial cells: The soluble form is more effective than the membrane-bound form. J. Immunol., 170:3954-3962, 2003. PubMed
Gelderman, M.P., Charukamnoetkanok, P., Brady, J.P., Hung, L., Zigler, J.S., Jr., Wawrousek, E.F., Vistica, B.P., Fortin. E., Chan, C.-C., and Gery, I.: A novel inflammatory eye disease induced by lymphocytes from knockout mice sensitized against the deleted ocular antigen. Clin. Exp. Immunol., 133:177-181, 2003. PubMed
Yu, C.-R., Mahdi, R.M., Ebong, S., Vistica, B.P., Gery, I., and Egwuagu, C.E.: Suppressor of cytokine signaling 3 regulates proliferation and activation of T-helper cells. J. Biol. Chem., 278:29752-29579, 2003. PubMed
Charukamnoetkanok, P., Brady, J.P., Wawrousek, E.F., Egwuagu, C.E., Zigler, J.S., Jr., Vistica, B.P., Whitcup, S.M., and Gery, I.: Immunotolerance toward native aA-crystallin in knockout mice deficient in the functional protein. Immunol. Lett., 89:259-265, 2003. PubMed
Ham, D.-I. Kim, S., Chen, J., Vistica, B.P., Farris, R.N., Lee, R.S., Wawrousek, E.F., Takase, H., Yu, C.-R., Egwuagu, C.E., Chan, C.-C., and Gery, I.: Central immunotolerance in transgenic mice expressing a foreign antigen under control of the rhodopsin promoter. Invest. Ophthalmol. Vis. Sci., 45:857-862, 2004. PubMed
Yu, C.-R., Mahdi, R.M., Ebong, S., Vistica, B.P., Chen, J., Guo, Y., Gery, I. and Egwuagu, C.E.: Proliferation and STAT6 Signaling Pathways are Negatively Regulated in T-helper Cells by STAT1 and Suppressors of Cytokine Signaling (SOCS). J. Immunol., 173: 737-746, 2004. PubMed
Tuo, J., Smith, B., Chew, E., Bojanowski. C.M., Meleth, A.D., Csaky, K., Gery, I. and Chan, C.-C.: The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration. FASEB J. 18:1297-1299, 2004. PubMed
Chen, J., Vistica, B.P., Takase, H., Ham, D.-I., Fariss, B.N., Wawrousek, E.F., Chan, C.-C., DeMartino, J.A., Farber, J.M. and Gery, I.: A unique pattern of up- and down-regulation of chemokine receptor CXCR3 on inflammation-inducing Th1 cells. Europ. J. Immunol. 34:2885-2894, 2004. PubMed
Ledee, D.R., Chen, J., Tonelli, L.H., Takase, H., Gery, I. and Zelenka, P.: Differential expression of splice variants of chemokine CCL27 mRNA in lens, cornea, and retina of the normal mouse eye. Mol. Vis. 10:663-667, 2004. PubMed
Chen, J., Vistica, B.P., Wiggert, B., Chan, C.-C., and Gery, I: The immunomodulator vasoactive intestinal peptide (VIP) does not affect experimental autoimmune uveitis (EAU) in B10.RIII mice. Ocul. Immunol. Inflam., 13:13-17, 2005. PubMed
Lim, W.-K., Fujimoto, C., Ursea, R., Mahesh, S.P., Silver, P., Chan, C.-C., Gery, I., and Nussenblatt, R.B.: Interleukin-1 receptor antagonist suppresses immune-mediated ocular inflammation in mice. Arch. Ophthalmol., 123:957-963, 2005. PubMed
Takase, H., Yu, C.-R., Mahdi, R.M., Douek, D.C., DiRusso, G.B., Midgley, F.M., Dogra, R., Allende, G., Rosenkranz, E., Pugliese, A., Egwuagu, C.E., and Gery, i.: Thymic expression of peripheral tissue antigens in humans:a remarkable variability among individuals. Inter. Immunol., 17:1131-1140, 2005. PubMed
Takase, H., Yu, C.-R., Liu, X., Fujimoto, C., Gery, I. And Egwuagu, C.E.: Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): Potential neuroprotective role of SOCS proteins. J. Neuroimmunol., 168:118-127, 2005 PubMed
