title: αβ TCR⁺ T cells, but not B cells, promote autoimmune keratitis in b10 mice lacking γδ T cells.
abstract: OBJECTIVE
  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.affiliation: Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA. obrienr@njhealth.org
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Chain
authors.forename: M Kemal
authors.initials: MK
authors.lastname: Aydintug
authors.forename: Dawn
authors.initials: D
authors.lastname: Bohrer-Kunter
authors.forename: Yafei
authors.initials: Y
authors.lastname: Huang
authors.forename: Ian R
authors.initials: IR
authors.lastname: Hardy
authors.forename: John C
authors.initials: JC
authors.lastname: Cambier
authors.forename: Kevin
authors.initials: K
authors.lastname: Lahmers
authors.forename: Tanja
authors.initials: T
authors.lastname: Nuhsbaum
authors.forename: Richard
authors.initials: R
authors.lastname: Davidson
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015352:Dry Eye Syndromes / Q000276:immunology; D005260:Female; D007634:Keratitis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency*; D013601:T-Lymphocytes / Q000276:immunology*; D013666:Tears / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta