γδ T cells are required for maximal expression of allergic conjunctivitis

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.