The fall of a Dogma? Unexpected high T-cell memory response to staphylococcus aureus in humans

Abstract

Introduction: Though Staphylococcus aureus is a major pathogen, vaccine trials have failed. In contrast, classs-witched 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 3H-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.