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
The Journal of Immunology, 2014•journals.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 …
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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