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S. R. Planck, M. J. Hall, W. Zhong, J. T. Rosenbaum, Z. Zhang; Synergism of Transgenic T and B Cells in MOG-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):826.
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Anti-B cell antibodies are clinically efficacious in treating some autoimmune diseases that are generally considered T cell-mediated. In line with this observation, double transgenic mice carrying both T and B cells specific for myelin oligodendrocyte glycoprotein (MOG) exhibit more severe multiple sclerosis (MS)-like encephalomyelitis and optic neuritis than mice transgenic for only T or only B cells. Uveitis is an extra-neurological complication of MS, and the degree of individual and coordinated influences of these two lymphocyte populations on ocular inflammation is unknown. We used an adoptive transfer, MOG-induced uveitis model to determine the impact of antigen-specific T and B cells during the ocular inflammation.
T cells of 2D2 mice and B cells of Th mice specifically react to MOG35-55. Donor 2D2 and Th mice received subcutaneous injection of 200 µg MOG peptide, 400 µg M. tuberculosis in complete Freund’s adjuvant, and 200 ng Pertussis toxin. 7 days later, T and B lymphocytes were isolated from spleens of these mice. Fifteen million 2D2 T cells or Th B lymphocytes were adoptively transferred to naïve albino C57BL/6 mice via a tail vein injection. Then, the recipient mice were intravitreally challenged with 10 µg MOG peptide and 200 ng LPS. 24 hours after the uveitis induction, ocular inflammation was examined by intravital microscopy. In some studies, albino Th mice were immunized with the MOG peptide for 14 days as above. Following adoptive transfer of 1.5 x 107 MOG-primed 2D2 T cells, these mice received intravitreal injections of MOG and LPS and were monitored as above.
Naïve wild-type mice that received Th B cells developed intraocular inflammatory cell infiltration in response to the MOG stimulation. However, adoptive transfer of 2D2 T cells displayed a more substantial eye inflammation. Next, we evaluated the cooperative effect of T and B cells. Compared to wild-type recipients or immunized Th mice without adoptive transfer of 2D2 cells, the Th mice that received 2D2 T cells developed a more severe uveitis.
These results support the hypothesis that separate transfer of transgenic B or T cells promotes the autoimmune uveitis with T cells having a more pronounced effect. In the context of a clinically more relevant scenario, T and B cells work in concert to exert a greater impact on a developing immunopathologic response.
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