Evidence that CD8⁺ dendritic cells enable the development of γδ T cells that modulate airway hyperresponsiveness

Airway hyperresponsiveness (AHR), a hallmark of asthma and several other diseases, can be modulated by γδ T cells. In mice sensitized and challenged with OVA, AHR depends on allergen-specific αβ T cells; but Vγ1⁺ γδ T cells spontaneously enhance AHR, whereas Vγ4⁺ γδ T cells, after being induced by airway challenge, suppress AHR. The activity of these γδ T cell modulators is allergen nonspecific, and how they develop is unclear. We now show that CD8 is essential for the development of both the AHR suppressor and enhancer γδ T cells, although neither type needs to express CD8 itself. Both cell types encounter CD8-expressing non-T cells in the spleen, and their functional development in an otherwise CD8-negative environment can be restored with transferred spleen cell preparations containing CD8⁺ dendritic cells (DCs), but not CD8⁺ T cells or CD8^- DCs. Our findings suggest that CD8⁺ DCs in the lymphoid tissues enable an early step in the development of γδ T cells through direct cell contact. DC-expressed CD8 might take part in this interaction.