Taylor, Amanda L and Llewelyn, Martin J (2010) Superantigen-induced proliferation of human CD4+CD25- T cells is followed by a switch to a functional regulatory phenotype. Journal of Immunology, 185 (11). pp. 6591-6598. ISSN 0022-1767
Full text not available from this repository.Abstract
Bacterial superantigens are potent T cell activators. In humans they cause toxic shock and scarlet fever, and they are implicated in Kawasaki's disease, autoimmunity, atopy, and sepsis. Their function remains unknown, but it may be to impair host immune responses increasing bacterial carriage and transmission. Regulatory (CD25(+)FOXP3(+)) T cells (Tregs) play a role in controlling inflammatory responses to infection. Approximately 2% of circulating T cells are naturally occurring Tregs (nTregs). Conventional Ag stimulation of naive FOXP3(-) T cells induces Ag-specific Tregs. Polyclonal T cell activation has been shown to produce non-Ag-specific Tregs. Because superantigens are unique among microbial virulence factors in their ability to trigger polyclonal T cell activation, we wanted to determine whether superantigen stimulation of T cells could induce non-Ag-specific Tregs. We assessed the effect of superantigen stimulation of human T cells on activation, regulatory markers, and cytokine production by flow cytometry and T cell suppression assays. Stimulation of PBMCs with staphylococcal exotoxin A and streptococcal pyrogenic exotoxins A and K/L resulted in dose-dependent FOXP3 expression. Characterization of this response for streptococcal pyrogenic exotoxin K/L confirmed its V beta specificity, that CD25(+)FOXP3(+) cells arose from CD25(-) T cells and required APCs. These cells had increased CTLA-4 and CD127 expression, typical of the recently described activated converted Treg-like cells, and exhibited functional suppressor activity comparable to nTregs. Superantigen-stimulated CD25(+)FOXP3(+) T cells expressed IL-10 at lower superantigen concentrations than was required to trigger IFN-gamma production. This study provides a mechanism for bacterial evasion of the immune response through the superantigen induction of Tregs.
Item Type: | Article |
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Schools and Departments: | Brighton and Sussex Medical School > Clinical and Experimental Medicine Brighton and Sussex Medical School > Global Health and Infection |
Subjects: | Q Science > QR Microbiology > QR0180 Immunology |
Depositing User: | Grecia GarciaGarcia |
Date Deposited: | 15 Aug 2011 11:30 |
Last Modified: | 21 Sep 2017 14:09 |
URI: | http://sro.sussex.ac.uk/id/eprint/7213 |
Google Scholar: | 6 Citations |