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Rapid ?? T-cell responses orchestrate innate immunity in response to Staphylococcal enterotoxin A.

ABSTRACT: In the generation of a traditional immune response against invading pathogens, innate cells guide T cells by programming their differentiation. However, here we demonstrate that ?? T cells have an essential role in priming innate immunity in the lung after Staphylococcus aureus enterotoxin A (SEA) inhalation. We found that SEA induces waves of cellular activation, cytokine production, and migration into the lung tissue and airways. However, this innate response was completely inhibited in the absence of ?? T cells. Specifically, we found that interleukin (IL)-17A was required for the recruitment of neutrophils and monocytes into the lung. The cellular source of IL-17A was ?? T cells, which increased their IL-17A production following SEA but only in an ?? T-cell-dependent manner. Thus, rapid T-cell activation orchestrates innate immunity and may be a new point of therapeutic intervention for acute lung injury.

SUBMITTER: Kumar S

PROVIDER: S-EPMC3722268 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Rapid αβ T-cell responses orchestrate innate immunity in response to Staphylococcal enterotoxin A.

Kumar S S Colpitts S L SL Ménoret A A Budelsky A L AL Lefrancois L L Vella A T AT

Mucosal immunology 20130116 5

In the generation of a traditional immune response against invading pathogens, innate cells guide T cells by programming their differentiation. However, here we demonstrate that αβ T cells have an essential role in priming innate immunity in the lung after Staphylococcus aureus enterotoxin A (SEA) inhalation. We found that SEA induces waves of cellular activation, cytokine production, and migration into the lung tissue and airways. However, this innate response was completely inhibited in the ab ...[more]

PMID: 23321986

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Project description:Toxic shock syndrome (TSS) is capable of inducing life-threatening fever, rash, and systemic organ failure, though the specific mechanisms behind these symptoms remain poorly understood. Staphylococcal enterotoxin B (SEB) and other superantigens have shown to be important factors in TSS, capable of promoting cross-linking between T cell receptors and major histocompatibility complexes which results in overwhelming T cell activation, proliferation, and cytokine production. The resulting proinflammatory cytokine cascade, often referred to as the "cytokine storm," seems to be critical to the development of disease. Interestingly, clinical studies have shown that children exhibit less severe TSS-associated morbidity than adults, though the mechanism behind this phenomenon has not been addressed. Indeed, despite the fact that most novel antigen exposure occurs early in life, be it from environmentally acquired pathogens or routine vaccination, normal pediatric T cell immune functions remain critically underexplored. This is largely due to difficulty in obtaining enough samples to explore more than a narrow sliver of the cell-mediated immune compartment. To address this limitation, we optimized a T effector (Teff)/circulating T follicular helper (cTFH) cell mass cytometry panel which allowed us to analyze a wide array of T cell populations and effector functions following in vitro SEB stimulation. We show that T cell activation-as measured by CD69 expression-following SEB stimulation is lower in pediatric participants, increasing throughout childhood, and reaching adult levels by around 15?years old. Further, while individual CD4+ effector memory T cell (TEM) effector molecules show limited age-associated differences following SEB stimulation, multifunctional CD4+ TEM are shown to positively correlate with increasing age through adolescence. Individual CD8+ TEM effectors and multifunctional phenotypes also show very strong age-associated increases following SEB stimulation. SEB stimulation has little impact on cTFH activation or functional cellular markers, regardless of age. These results, coupled with the fact that a robust proinflammatory cytokine response seems critical to developing severe TSS, suggest a possible connection between the significantly reduced T cell activation and multifunctional populations following in vitro SEB stimulation in our pediatric participants and clinical observations relating to reduced TSS mortality in children.

Dataset Information

Rapid ?? T-cell responses orchestrate innate immunity in response to Staphylococcal enterotoxin A.

Publications

Rapid αβ T-cell responses orchestrate innate immunity in response to Staphylococcal enterotoxin A.

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