γδ T Cells Are Required for Maximal Expression of Allergic Conjunctivitis

Abstract

PURPOSE: To determine the function of γδ T cells in early- and late-phase responses in allergic conjunctivitis.

METHODS: Wild-type (WT) C57BL/6 and γδ T cell-deficient (TCR-δ(-/-)) mice were immunized intraperitoneally and challenged topically for 7 consecutive days with short ragweed pollen. Natural killer T (NKT) and γδ T cell-double-deficient mice were generated by treating TCR-δ(-/-) mice with anti-CD1d antibody. Allergic conjunctivitis was evaluated clinically, and the late-phase response was assessed by histopathology. Cytokine profiles were evaluated by ELISA. The afferent and efferent arms of allergic conjunctivitis were assessed by adoptive transfer of CD4(+) T cells from WT or TCR-δ(-/-) mice into naive TCR-δ(-/-) or WT mice.

RESULTS: TCR-δ(-/-) mice had decreased clinical manifestations of allergic conjunctivitis compared with WT mice. TCR-δ(-/-) mice had decreased eosinophilic infiltration compared with WT mice. TCR-δ(-/-) mice produced less Th2-associated cytokines interleukin (IL)-4, -5, and -13 compared with WT mice. Clinical manifestations of allergic conjunctivitis were lowest in NKT cell-depleted TCR-δ(-/-) mice. However, late-phase allergic conjunctivitis in NKT cell-depleted, TCR-δ(-/-) mice was the same as TCR-δ(-/-) mice. Adoptive transfer of CD4(+) T cells revealed that γδ T cells are needed for the afferent and efferent arms of allergic conjunctivitis.

CONCLUSIONS: γδ T cells are needed for full expression of both the clinical manifestations and the late phase of allergic conjunctivitis. Thus, γδ T cells have an important impact in the expression of allergic conjunctivitis and are a potential therapeutic target in the management of allergic diseases of the ocular surface.