γδ T cells can play a role in provoking an inflammatory attack on the cornea

Abstract

Abstract Ocular immune privilege results from a complex set of mechanisms that together prevent immunogenic inflammation, but still allow the eye to deal with potentially infectious agents in a localized way that does not compromise vision. Failure of immune privilege can unleash a damaging autoimmune attack on the eye. γδ T cells have been found to be important for these processes in a number of different systems. In mice of the C57BL/10 background (B10), we have previously shown that γδ. T cells help prevent the spontaneous development of keratitis, an inflammation of the cornea that B10.TCRδ −/− mice are highly prone to develop, particularly the females. Paradoxically, B10 mice that can produce γδ T cells but not αβ T cells also develop keratitis at a high rate. We recently found that Vγ4+ cells from the spleens of keratitic B10.TCRβ−/− mice, but not Vγ1+ cells, can adoptively transfer the disease to normally keratitis-resistant B10.TCRβ−/−δ−/− hosts. Immunofluorescence staining of corneal whole mounts from B10.TCRβ−/− mice revealed that Vγ4+ cells infiltrate the keratitic corneas, and show a strong bias to secrete IL-17. In contrast, Vγ1+ cells were more rare in the keratitic corneas and did not produce IL-17. The majority of the γδ T cells in keratitic corneas were Vγ1-negative, Vγ4-negative, and Vγ7-negative, however, and did not produce IL-17. We hypothesize that although some γδ T cell subsets protect against autoimmune attack on the cornea, certain Vγ4+ γδ T cells instead promote keratitis by infiltrating the corneas and secreting IL-17, which attracts and mobilizes neutrophils, resulting in tissue damage.