Large-scale Early in vitro Response to Actinobacillus actinomycetemcomitans Suggests Superantigenic Activation of T-cells

Abstract

The mode of T-cell response to Actinobacillus actinomycetemcomitans is largely unknown. The present study sought to investigate the hypothesis that A. actinomycetemcomitans expresses superantigens, capable of antigen-non-specific T-cell activation. To that end, peripheral blood mononuclear cells were stimulated with A. actinomycetemcomitans, and T-cell expression of the early activation marker, CD69, was determined by flow cytometry. Results showed that A. actinomycetemcomitans activated a large number of T-cells with magnitude similar to that of staphylococcal enterotoxin superantigens. A. actinomycetemcomitans sonicate preferentially activated T-cells expressing Vbeta5.1 and Vbeta8, while the extracellular preparation activated Vbeta5.1+, Vbeta8+, and Vbeta12+ T-cells. T-cell response to A. actinomycetemcomitans was observed in the presence of autologous, as well as heterologous, antigen-presenting cells, suggesting a MHC-non-restricted response. Thus, the in vitro response to A. actinomycetemcomitans is characterized by large-scale T-cell activation in a Vbeta-specific and MHC-non-restricted manner, consistent with the involvement of superantigens.

High Incidence of Actinobacillus Actinomycetemcomitans Infection in Acute Coronary Syndrome

“…A. actinomycetemcomitans has been reported to produce an as yet unidentified superantigen that rapidly causes T-cell apoptosis. 33,34) Ten, et al reported that periodontitis patients infected with A. actinomycetemcomitans harbored A. actinomycetemcomitans-specific T-cells in peripheral blood, and T-cells expressed RANK ligand (RANKL) in response to A. actinomycetemcomitans. 35) RANKL from T-cells stimulates vascular smooth muscle cells (VSMC) to produce matrix metalloproteinase-9 (MMP-9), which destabilizes atherosclerotic plaques 36) and recently was reported to be elevated in coronary artery plaque in patients with acute myocardial infarction.…”

Characterization of the T-Cell Receptor Vβ Repertoire in the Human Immune Response againstLeishmaniaParasites

“…Regarding V␤12 specifically, it has been shown that staphylococcal enterotoxin B preferentially induces the production of Th1 cytokines in TCR V␤12 T cells from healthy subjects and the production of Th2 cytokines in cells from atopic dermatitis patients (26). Also, an Actinobacillus actinomycetemcomitans extracellular preparation activated TCR V␤12 T cells (54). The identification of similar antigens in Leishmania is still deficient, probably due to the complexity of infection.…”

Anti‐Neutrophil Cytoplasmic Autoantibodies: A Renewed Paradigm in Periodontal Disease Pathogenesis?

“…Recently, a study by Leung and Torres 35 demonstrated that P. intermedia strain 17, which is a clinical isolate, induced the strongest expansion of CD4 + T‐cell subsets that express Vβ8, Vβ12, and Vβ17 TCRs. Furthermore, to confirm the role of A. actinomycetemcomitans –derived SAg, Zadeh et al 36 conducted an in vitro study using peripheral blood mononuclear cells. These cells were stimulated with A. actinomycetemcomitans , and T cells expressing an early activation marker, namely CD69, were demonstrated through flow cytometry–based detection.…”

“…They further reported that the response to this bacterial stimulus was a large‐scale T‐cell activation in a Vβ‐specific manner demonstrating the superantigenic property by A. actinomycetemcomitans. 36 …”