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

JB Kolata, I Kühbandner, C Link… - The Journal of …, 2015 - academic.oup.com
JB Kolata, I Kühbandner, C Link, N Normann, CH Vu, L Steil, C Weidenmaier, BM Bröker
The Journal of infectious diseases, 2015academic.oup.com
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 …
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 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.
Oxford University Press