Staphylococcus aureus infection of mice expands a population of memory γδ T cells that are protective against subsequent infection

AG Murphy, KM O'Keeffe, SJ Lalor… - The Journal of …, 2014 - journals.aai.org
AG Murphy, KM O'Keeffe, SJ Lalor, BM Maher, KHG Mills, RM McLoughlin
The Journal of Immunology, 2014journals.aai.org
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 …
Abstract
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 γδ 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 Vγ4+ subset and accumulate at the site of infection subsequent to an initial Vγ1. 1+ and Vγ2+ T cell response. Moreover, these Vγ4+ 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 γδ T cell activation during the primary infection, IL-1 signaling was dispensable for activation and expansion of memory γδ T cells upon re-exposure to S. aureus. Our findings demonstrate that a γδ T cell memory response can be induced upon exposure to S. aureus, in a fashion analogous to that associated with classical αβ T cells, and suggest that induction of IL-17–expressing γδ T cells may be an important property of a protective vaccine against S. aureus.
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