Figure 2.
Uveitis in aire-deficient animals is T cell dependent, and increased frequencies of IRBP-specific T cells arise in aire-deficient animals. Immunostaining of frozen eye sections from aire-deficient mice with cell surface markers identifies CD4+ T cells as the predominant cells within the mononuclear infiltrate. (A) CD8+ T cells and IgD+ B cells are also present in the retina. (B) No infiltrate was observed in the eyes of age-matched, aire-sufficient animals. (C) Eye disease can be transferred with a pooled population of splenocytes and cervical lymph node cells from aire-deficient animals. Cells devoid of (E) CD8+ T cells but not (D) CD4+ T cells are capable of transferring disease into immunodeficient hosts. T cells were purified from cervical lymph nodes from unimmunized aire-deficient and age- and sex-matched aire wild-type controls in the C57BL/6 background (18–20 wk old). (F) T cells were assayed in an ELISPOT assay for IFN-γ production in the presence of 10 μg/ml IRBP, media alone, or 10 μg/ml OVA in the presence of APCs (ConA was also tested as a positive control; not depicted). Open circles represent individual aire-deficient animals; the solid line indicates the mean value. Closed circles represent individual aire-sufficient animals; the dashed line indicates the mean value. For IRBP and media alone, n = 7 animals per group; the number of spots for IRBP was statistically significant (P = 0.0023) for aire-deficient compared with aire-sufficient animals. For the OVA control, n = 3 animals per group.