Send to

Choose Destination
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

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


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center