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Immunology. 2012 Feb;135(2):158-67. doi: 10.1111/j.1365-2567.2011.03529.x.

Induction of contact-dependent CD8(+) regulatory T cells through stimulation with staphylococcal and streptococcal superantigens.

Author information

1
Division of Clinical Medicine, Brighton and Sussex Medical School, Falmer, UK.

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.

PMID:
22043981
PMCID:
PMC3277718
DOI:
10.1111/j.1365-2567.2011.03529.x
[Indexed for MEDLINE]
Free PMC Article

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