Vγ1+ γδ T cells reduce IL-10-producing CD4+CD25+ T cells in the lung of ovalbumin-sensitized and challenged mice

In OVA-sensitized and challenged mice, γδ T cells expressing Vγ1 enhance airway hyperresponsiveness (AHR) but the underlying mechanism is unclear. These cells also reduce IL-10 levels in the airways, suggesting that they might function by inhibiting CD4+CD25+ regulatory T cells (Treg) or other CD4+ T cells capable of producing IL-10 and suppressing AHR. Indeed, sensitization and challenge with OVA combined with inactivation of Vγ1+ cells increased CD4+CD25+ cells in the lung, and markedly those capable of producing IL-10. The cellular change was associated with increased IL-10 and TGF-β levels in the airways, and a decrease of IL-13. Treg include naturally occurring Foxp3+ Treg, inducible Foxp3− Treg, and antigen-specific Treg many of which express folate receptor 4 (FR4). Although Foxp3 gene expression in the lung was also increased pulmonary CD4+ T cells, expressing Foxp3-protein or FR4 remained stable. Therefore, the inhibition by Vγ1+ γδ T cells might not be targeting Foxp3+ Treg but rather CD4+ T cells destined to produce IL-10.