Memory gamma delta T cells are activated by APCs in the mLN following oral Listeria monocytogenes infection

ROMAGNOLI PA; SHERIDAN BS; DICKINSON M; PHAM QM; LEFRANCOIS L

Honolulu, HI

Congreso; AAI IMMUNOLOGY 2013; 2013

The American Association of Immunologists, Inc.

Infection with bacterial pathogens can disrupt the intestinal mucosa that maintains a healthy immune system while keeping bacteria at bay. Using a model of oral infection with a murinized form of Listeria monocytogenes (Lm), our lab has identified a gamma delta T cell population that forms bona-fide memory and provides protection from re-infection. Since the precise mechanism of activation of most gamma delta T cells has remained elusive, we investigated the requirements for antigen presenting cells (APCs) in the activation of Lm-induced memory gamma delta T cells. Here, we show that several cells in the mesenteric lymph node (mLN), including dendritic cells (DCs), inflammatory monocytes and granulocytes, can act in conjunction to activate gamma delta T cells to express IL-17A, IFN-γ or both and induced their proliferation. This activation was largely cell contact dependent, but was augmented by soluble factors at the peak of primary and secondary gamma delta T cell responses, mainly by IL-1 beta but partially by IL-2 and IL-23. Moreover, using confocal microscopy we were able to image Lm-induced gamma delta T cells interacting with DCs and inflammatory monocytes in the interfollicular area of the mLNs soon after Lm challenge infection. We believe these results not only advance the understanding of gamma delta T cell biology, but also provide novel strategies to design protective vaccines for the intestinal mucosa..