CD30 ligand (CD30L, CD153), a member of the TNF superfarnily, and its receptor CD30are important for differentiation and activation of CD4+ Th17 cells.In the present report, we demonstrate that the IL-17A-producing γδ T cells normally developed in the fetal thymus, whereas Vγ1-Vγ4-γδ T cells expressed Vγ6/Vδ1 gene transcript selectively decreased in mucosa-associated tissues in na(i)ve CD30KO or CD30LKO mice.Moreover, CD30 and CD30L were expressed preferentially by Vγ1-Vγ4-γδ T cells in na(i)ve mice.The bacteria clearance was attenuated by the impaired response of the IL-17A-producing γδ T cells and decreased infiltration of neutrophils in CD30KO or CD30LKO mice.In vivo administration of agonistic anti-CD30 mAb restored the ability of protection against L.monocytogenes by enhancing Vγ1-Vγ4-γδ T cells producing IL-17A not only in WT but also CD30LKO mice.Taken together, it appears that CD30L/CD30 signaling plays an important role in the maintenance and activation of IL-17A-producing γδ T cells presumably bearing Vγ6 in the mucosa-associated tissues of mice.