γδ T cells play a protective role during infection with Nippostrongylus brasiliensis by promoting goblet cell function in the small intestine

The intestinal epithelium is rich in gamma delta T cells and the gut is a site of residence for a wide variety of pathogens, including nematodes. Although CD4(+) T-cell receptor (TCR) -alpha beta(+) T helper type 2 T cells are essential for the expulsion of intestinal nematodes, little information is available on the function of gamma delta T cells in this type of infection. Here, we demonstrate two major functions of gamma delta T cells as a potently protective T-cell population against Nippostrongylus brasiliensis infection using gamma delta T-cell-deficient (TCR-delta(-/-)) mice. First, gamma delta T cells are required to initiate rapid expulsion of adult worms from the intestine and to limit egg production. Second, gamma delta T cells prevent the pathological intestinal damage associated with nematode infection, evident by increased clinical disease and more severe microscopic lesions in infected TCR-delta(-/-) mice. gamma delta T-cell deficiency led to delayed goblet cell hyperplasia in association with reduced expression of phosphorylated STAT6, MUC2, Trefoil factor-3 (TFF3) and T helper type 2 cytokines including interleukin-13 (IL-13). TCR-delta(-/-) mice also produced more interferon-gamma than wild-type mice. Within the intraepithelial lymphocyte compartment, gamma delta T cells produced IL-13. Adoptive transfer of gamma delta T cells or administration of recombinant IL-13 to TCR-delta(-/-) mice successfully reduced the egg production by N. brasiliensis. Collectively, these data provide strong evidence that gamma delta T cells play an important role in controlling infection with intestinal nematodes and limiting infection-induced pathology.