Literature DB >> 22199243

αβ TCR⁺ T cells, but not B cells, promote autoimmune keratitis in b10 mice lacking γδ T cells.

Rebecca L O'Brien1, 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.   

Abstract

PURPOSE: To investigate additional factors in the spontaneous development of keratitis previously reported in B10.TCRδ⁻/⁻ female mice.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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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Year:  2012        PMID: 22199243      PMCID: PMC3292366          DOI: 10.1167/iovs.11-8855

Source DB:  PubMed          Journal:  Invest Ophthalmol Vis Sci        ISSN: 0146-0404            Impact factor:   4.799


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