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S. R. Planck, T. Kawaguchi, E. E. Vance, J. T. Rosenbaum; A Novel Model to Study the Interaction of T Cells and B Cells in Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2654.
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Current models of autoimmune uveitis are generally considered to be T cell dependent. Cytotoxic therapy directed at B cells is gaining traction for several immune mediated diseases such as rheumatoid arthritis and multiple sclerosis. We sought to develop a model of autoimmune uveitis in which the contribution of B cells could be investigated.
2D2 mice, whose T cells recognize myelin oligodendrocyte glycoprotein peptide35-55 (MOG) and Th mice whose B cells recognize the same peptide, were crossed with mice that express a fluorescent protein under an actin promoter so that lymphocytes could be readily tracked by intravital epifluorescent microscopy. In some studies lymphocytes from these mice were transferred to C57BL/6 mice that lack tyrosinase so that pigment, which interferes with the detection of fluorescence, was not present in the iris. T or B cells were isolated from the spleen by negative selection.
Immunization of C57BL/6 mice with MOG peptide induced paralysis secondary to demyelination and this disease is known to be exacerbated if either MOG-specific T or B cells are present and most severe if both are present. Iritis was not detected in this model. Passive transfer of 20 million MOG-specific naïve T cells also did not produce iritis even if MOG was injected intravitreally. However, 2D2 T cells infiltrated the iris if they either were derived from a mouse immunized with MOG or stimulated with MOG in vitro, and after transfer, the eye was challenged intravitreally with both10 µg MOG and 250 ng endotoxin. Challenge with endotoxin alone induced minimal 2D2 T cell infiltration. The iris infiltration by 2D2 T cells persisted for more than 2 days. Iritis was also induced by immunizing Th mice with MOG in complete Fruend’s adjuvant, on day 16 injecting endotoxin intraperitoneally, and 3 days later injecting MOG intravitreally. MOG-specific B cells themselves were not prominent within the iris when B cells from MOG-immunized Th mice were transferred to a C57BL/6 mouse which was then challenged with MOG and endotoxin intravitreally.
B cells could contribute to autoimmunity by a variety of mechanisms which include antigen presentation, cytokine-mediated modulation of the T cell response, or antibody-dependent effects. The availability of fluorescently tagged T and B cells recognizing the same peptide provides a unique tool that should allow clarification as to how B cells contribute to autoimmunity.
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