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Rebecca L. O'Brien, Jennifer L. Chain, M. Kemal Aydintug, Dawn Bohrer-Kunter, Yafei Huang, Ian R. Hardy, John C. Cambier, Kevin Lahmers, Tanja Nuhsbaum, Richard Davidson, Deming Sun, Willi K. Born; αβ TCR+ T Cells, but Not B Cells, Promote Autoimmune Keratitis in B10 Mice Lacking γδ T Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(1):301-308. doi: 10.1167/iovs.11-8855.
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To investigate additional factors in the spontaneous development of keratitis previously reported in B10.TCRδ−/− female mice.
The study tested whether susceptible B10.TCRδ−/− mice have dry eyes compared with resistant B6.TCRδ−/− females and also rederived the B10.TCRδ−/− strain to test for the role of an infectious agent. Also assessed was whether adoptive transfer of αβ T cells from autoimmune mice induced keratitis in resistant mice. In addition, a potential role was examined for B cells or autoantibodies by B-cell inactivation, and the role of female hormones was tested by ovariectomy. Finally, the study investigated whether adoptive transfer of Vγ1+ γδ T cells confers protection.
Tear production in B10.TCRδ−/− females was actually higher than in B6.TCRδ−/− controls. Rederived B10.TCRδ−/− mice still developed keratitis. Keratitis was induced in resistant mice after adoptive transfer of αβ T cells from keratitic donors. Inactivation of B cells from susceptible mice had no effect on the development of keratitis. Ovariectomy did not significantly reduce disease in B10.TCRδ−/− females. Adoptive transfer of Vγ1+ cells from wild-type donors reduced keratitis in B10.TCRδ−/− females.
Neither low tear levels nor ovarian hormones contribute to spontaneous keratitis in B10.TCRδ−/− female mice, nor does it appear to depend on an infectious agent carried vertically in this strain. However, αβ T cells from keratitic hosts are sufficient to induce disease in the resistant B10.TCRβ−/−δ−/− strain. Autoaggressive αβ T cells in the absence of Vγ1+ T cells in B10.TCRδ−/− mice may be insufficiently checked to prevent disease.
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