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

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.

• Authors: 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
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 53 Issue 1 Pg. 301-8 (Jan 25 2012) ISSN: 1552-5783 [Electronic] United States
• PMID: 22199243 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Autoantibodies
• Receptors, Antigen, T-Cell, alpha-beta
• Receptors, Antigen, T-Cell, gamma-delta

Topics

• 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)