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

• Published in: Investigative ophthalmology & visual science Vol. 53; no. 1; pp. 301 - 308
• Main Authors: O'Brien, Rebecca L, Chain, Jennifer L, Aydintug, M Kemal, Bohrer-Kunter, Dawn, Huang, Yafei, Hardy, Ian R, Cambier, John C, Lahmers, Kevin, Nuhsbaum, Tanja, Davidson, Richard, Sun, Deming, Born, Willi K
• Format: Journal Article
• Language: English
• Published: United States Association for Research in Vision and Ophthalmology, Inc 25-01-2012
• Subjects: Adoptive Transfer; Animals; Autoantibodies - immunology; Autoimmune Diseases - immunology; B-Lymphocytes - immunology; Dry Eye Syndromes - immunology; Female; Keratitis - immunology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Ovariectomy; Receptors, Antigen, T-Cell, alpha-beta - physiology; Receptors, Antigen, T-Cell, gamma-delta - deficiency; T-Lymphocytes - immunology; Tears - metabolism
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.11-8855

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.