Journal
JOURNAL OF IMMUNOLOGY
Volume 192, Issue 8, Pages 3697-3708Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1303420
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Funding
- Wellcome Trust Research Career Development Fellowship [WT086515MA]
- Science Foundation Ireland Investigator Project Grant [12/IP/1532]
- Science Foundation Ireland (SFI) [12/IP/1532] Funding Source: Science Foundation Ireland (SFI)
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The development of vaccines against Staphylococcus aureus has consistently failed in clinical trials, likely due to inefficient induction of cellular immunity. T cell-derived IL-17 is one of the few known correlates of antistaphylococcoal immunity, conferring protection against S. aureus infections through its ability to promote phagocytic cell effector functions. A comprehensive understanding of the discrete T cell subsets critical for site-specific IL-17-mediated bacterial clearance will therefore be necessary to inform the development of vaccines that efficiently target cellular immunity. In this study, we have identified a population of CD44(+)CD27(-) memory gamma delta T cells, expanded upon infection of C57BL/6 mice with S. aureus, which produce high levels of IL-17 and mediate enhanced bacterial clearance upon reinfection with the bacterium. These cells are comprised largely of the V gamma 4(+) subset and accumulate at the site of infection subsequent to an initial V gamma 1.1(+) and V gamma 2(+) T cell response. Moreover, these V gamma 4(+) T cells are retained in the peritoneum and draining mediastinal lymph nodes for a prolonged period following bacterial clearance. In contrast to its critical requirement for gamma delta T cell activation during the primary infection, IL-1 signaling was dispensable for activation and expansion of memory gamma delta T cells upon re-exposure to S. aureus. Our findings demonstrate that a gamma delta T cell memory response can be induced upon exposure to S. aureus, in a fashion analogous to that associated with classical alpha beta T cells, and suggest that induction of IL-17-expressing gamma delta T cells may be an important property of a protective vaccine against S. aureus.
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