Induction of contact-dependent CD8(+) regulatory T cells through stimulation with staphylococcal and streptococcal superantigens
| Autor: | Amanda L. Taylor, Elizabeth L. A. Cross, Martin J. Llewelyn |
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| Rok vydání: | 2011 |
| Předmět: |
Antigens
Bacterial Staphylococcus aureus Superantigens Streptococcus pyogenes ZAP70 Immunology FOXP3 hemic and immune systems chemical and pharmacologic phenomena Original Articles Biology CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory Microbiology Interleukin-10 Interleukin 21 Interferon-gamma Superantigen Immunology and Allergy Cytotoxic T cell Humans IL-2 receptor Antigen-presenting cell Interleukin 3 Cell Proliferation |
| Zdroj: | Immunology. 135(2) |
| ISSN: | 1365-2567 |
| Popis: | The bacterial superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes are potent stimulators of polyclonal T-cell proliferation. They are the causes of toxic shock syndrome but also induce CD25(+) FOXP3(+) regulatory cells in the CD4 compartment. Several studies have recently described different forms of antigen-induced regulatory CD8(+) T cells in the context of inflammatory diseases and chronic viral infections. In this paper we show that bacterial superantigens are potent inducers of human regulatory CD8(+) T cells. We used four prototypic superantigens of S. aureus (toxic shock syndrome toxin-1 and staphylococcal enterotoxin A) and Str. pyogenes (streptococcal pyrogenic exotoxins A and K/L). At concentrations below 1 ng/ml each toxin triggers concentration-dependent T-cell receptor Vβ-specific expression of CD25 and FOXP3 on CD8(+) T cells. This effect is independent of CD4(+) T-cell help but requires antigen-presenting cells for maximum effect. The cells also express the activation/regulatory markers cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumour necrosis factor receptor-related protein and skin homing adhesins CD103 and cutaneous lymphocyte-associated antigen. Superantigen-induced CD25(+) FOXP3(+) CD8(+) T cells were as potent as freshly prepared naturally occurring CD4(+) regulatory T cells in suppressing proliferation of CD4(+) CD25(-) T cells in response to anti-CD3 stimulation. Although superantigen-induced CD8(+) CD25(+) FOXP3(+) express interleukin-10 and interferon-γ their suppressive function is cell contact dependent. Our findings indicate that regulatory CD8(+) T cells may be a feature of acute bacterial infections contributing to immune evasion by the microbe and disease pathogenesis. The presence and magnitude of regulatory CD8(+) T-cell responses may represent a novel biomarker in such infections. Superantigen-induced regulatory CD8(+) T cells also have therapeutic potential. |
| Databáze: | OpenAIRE |
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