The Fall of a Dogma? Unexpected High T-Cell Memory Response to Staphylococcus aureus in Humans.
BACKGROUND
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.
Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald.
Julia B
JB
Kolata
Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald.
Iris
I
Kühbandner
Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald.
Christopher
C
Link
Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald.
Nicole
N
Normann
Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald.
Chi Hai
CH
Vu
Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald.
Leif
L
Steil
Interfaculty Institute for Microbiology and Infection Medicine Tübingen, Eberhard-Karls-University, Germany.
Christopher
C
Weidenmaier
Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald.
Barbara M
BM
Bröker
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007553:Isotope Labeling; D007963:Leukocytes, Mononuclear / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D016207:Cytokines
S. aureus; cytokines; human T-cells; memory response; proliferation