The Fall of a Dogma? Unexpected High T-Cell Memory Response to Staphylococcus aureus in Humans

J Infect Dis. 2015 Sep 1;212(5):830-8. doi: 10.1093/infdis/jiv128. Epub 2015 Mar 3.

Abstract

Introduction: Though Staphylococcus aureus is a major pathogen, vaccine trials have failed. In contrast, class-switched antibodies specific to S. aureus are common, implying immune memory formation and suggesting a large pool of S. aureus-reactive helper T-cells.

Objective: To elucidate the cellular arm of S. aureus-specific immune memory, the T-cell response in humans was characterized.

Methods: The proliferative response of human peripheral blood mononuclear cells (PBMCs) to S. aureus antigens and the frequency of S. aureus-specific T-cells were quantified by (3)H-thymidine incorporation; cytokine release was measured by flow cytometry.

Results: Staphylococcus aureus particles and extracellular proteins elicited pronounced proliferation in PBMCs of healthy adults. This reflected a memory response with high frequencies of T-cells being activated by single S. aureus antigens. The whole S. aureus-specific T-cell pool was estimated to comprise 3.6% of T-cells with 35-fold differences between individuals (range, 0.2%-5.7%). When exposed to S. aureus antigens, the T-cells released predominantly but not solely T helper (Th)1/Th17 cytokines.

Conclusions: The large number of S. aureus antigen-reactive memory T-lymphocytes is likely to influence the course of S. aureus infection. To enable rational vaccine design, the naturally acquired human T-cell memory needs to be explored at high priority.

Keywords: S. aureus; cytokines; human T-cells; memory response; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology
  • Cell Proliferation
  • Cytokines / metabolism
  • Flow Cytometry
  • Humans
  • Immunologic Memory*
  • Isotope Labeling
  • Leukocytes, Mononuclear / immunology
  • Staphylococcus aureus / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Bacterial
  • Cytokines