title: Induction of contact-dependent CD8(+) regulatory T cells through stimulation with staphylococcal and streptococcal superantigens.
abstract: 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.
authors: Division of Clinical Medicine, Brighton and Sussex Medical School, Falmer, UK.
authors: Amanda L
authors: AL
authors: Taylor
authors: Elizabeth L A
authors: EL
authors: Cross
authors: Martin J
authors: MJ
authors: Llewelyn
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology* / Q000302:isolation & purification; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000276:immunology* / Q000302:isolation & purification; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000302:isolation & purification; D018089:Superantigens / Q000276:immunology* / Q000302:isolation & purification; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D018089:Superantigens; D016753:Interleukin-10; D007371:Interferon-gamma