Multifunctional and protective memory γδ T cells in intestinal tissues (P3227)

Abstract

Abstract Recently, studies in humans have suggested that γδ T cells may play a role in adaptive immunity. Surprisingly, oral Listeria monocytogenes (Lm) infection of mice induced a unique population of CD27neg CD44high Vγ4+ γδ T cells in the mesenteric lymph nodes (MLN) and lamina propria that was maintained into memory and capable of rapid expansion following secondary infection. Lm-elicited γδ T cells were mobilized into the blood and upregulated the gut homing receptor α4β7 but failed to migrate into the epithelium. The responding γδ T cells produced IL-17A and IFNγ and expressed T-bet and RORγt. Cytokine expression from memory γδ T cells could be induced by MLN from 2 dpi mice and was reduced by depletion of MHC II-expressing cells. Moreover, batf3-/- mice failed to induce γδ T cell expansion suggesting a role for migrant APCs in the activation of Lm-elicited γδ T cells. Interestingly, Lm-elicited memory γδ T cells failed to expand to i.v. Lm infection or oral Salmonella infection suggesting contextual specificity to the priming pathogen. In the absence of αβ T cell control, memory γδ T cells are the predominate source of protection and limit bacterial burden through enhanced expansion and cytokine production. While depletion of αβ T cells or γδ TCR internalization had little effect on protection, coupling treatments completely abrogated protection in intestinal tissues. Thus, γδ T cells are capable of generating a protective mucosal memory population following oral Lm infection.