Multifunctional and protective memory {gamma}{delta} T cells in intestinal tissues

SHERIDAN BS; ROMAGNOLI PA; PHAM QM; FU HH; ALONZO F 3RD; SCHUBERT WD; FREITAG NE; LEFRANCOIS L

Honolulu, HI

Congreso; AAI IMMUNOLOGY 2013; 2013

The American Association of Immunologists, Inc.

Recently, studies in humans have suggested that gamma delta T cells may play a role in adaptive immunity.Surprisingly,oral Listeria monocytogenes (Lm) infection of mice induced a unique population of CD27negCD44high Vgamma 4+ T cells in the mesenteric lymph nodes (MLN) and lamina propria that was maintainedinto memory and capable of rapid expansion following secondary infection. Lm-elicited gamma delta T cellswere mobilized into the blood and upregulated the gut homing receptor alpha 4 beta 7 but failed to migrateinto the epithelium. The responding gamma delta T cells produced IL-17A and IFN gamma and expressed T-bet and RORγt.Cytokine expression from memory gamma delta T cells could be induced by MLN from 2dpi mice and was reduced by depletion of MHC II-expressing cells. Moreover, batf3-/-mice failed to inducegamma delta T cell expansion suggesting a role for migrant APCs in the activation of Lm-elicited gammadelta T cells. Interestingly, Lm-elicited memory gamma delta T cells failed to expand to i.v. Lm infection ororal Salmonella infection suggesting contextual specificity to the priming pathogen. In the absence of alphabeta T cell control, memory gamma delta T cells are the predominate source of protection and limit bacterialburden through enhanced expansion and cytokine production. While depletion of alpha beta T cells or gammadelta TCR internalization had little effect on protection, coupling treatments completely abrogated protectionin intestinal tissues. Thus, gamma delta T cells are capable of generating a protective mucosal memorypopulation following oral Lm infectio.