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N.D. Heuss, C. Dou, D.S. Gregerson; Spontaneous Immunoregulation Induced by Retinal Expression of Antigen Differs From Immune Deviation Induced by Inoculation of Antigen . Invest. Ophthalmol. Vis. Sci. 2003;44(13):742.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We recently reported that transgenic expression of an antigen in the retina resulted in the presence of an immunoregulatory response that was detected by inhibition of the DTH response in mice immunized with the same antigen. Since the immune deviation response induced by inoculation of antigen into the eye also leads to inhibition of DTH, other properties of the spontaneous and induced responses were compared and contrasted to learn if similar mechanisms are responsible for both observations. Methods: The responses of normal mice and retinal beta-galactosidase (b-gal) expressing mice were compared in animals treated to induce immune deviation, or that were untreated (to allow assessment of the endogenous regulatory activity). After ear testing for DTH, spleen cells were collected for cytokine assays and serum was collected for antibody testing. For adoptive transfer of the endogenous regulatory response, spleen cells, or specific fractions of spleen cells prepared by magnetic separation, were transferred into normal, non-transgenic mice. Results: Using adoptive transfer, the endogenous response was found to differ from immune deviation (ACAID) in that the endogenous regulation had little effect on on-going responses; the regulatory cells must be present at the time of immunization. The cells which transfer the endogenous regulation were enriched in the Thy-1+ population of spleen. Separation of spleen into MHC class II+ vs – populations had no effect. Of several cytokines we have tested, only IFN-gamma is dramatically different between immune deviation (IFN-gamma is greatly reduced) and the endogenous response (IFN-gamma is not affected). IL-10, and TGF-beta are slightly higher in the endogenous response, but IL-4 is higher in the induced immune deviation (ACAID). The total b-gal specific IgG response is not much affected by the endogenous regulatory response, and the skewing of the IgG1/IgG2 ratio is small. Conclusions: The immunoregulation resulting from endogenous retinal antigen expression differs from the immune deviation of ACAID in several respects.
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