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Superantigen-induced proliferation of human CD4+CD25- T cells is followed by a switch to a functional regulatory phenotype.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2010 Dec 01; Vol. 185 (11), pp. 6591-8. Date of Electronic Publication: 2010 Nov 03. - Publication Year :
- 2010
-
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 Vβ 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-γ production. This study provides a mechanism for bacterial evasion of the immune response through the superantigen induction of Tregs.
- Subjects :
- Dose-Response Relationship, Immunologic
Epitopes, T-Lymphocyte immunology
Forkhead Transcription Factors biosynthesis
Forkhead Transcription Factors genetics
Humans
Immunoglobulin Variable Region biosynthesis
Interleukin-10 biosynthesis
Interleukin-2 Receptor alpha Subunit biosynthesis
Interleukin-2 Receptor alpha Subunit metabolism
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Leukocytes, Mononuclear microbiology
Lymphocyte Activation immunology
Staphylococcus aureus immunology
Streptococcus pyogenes immunology
T-Lymphocytes, Regulatory microbiology
Antigens, Bacterial physiology
Cell Proliferation
Immunophenotyping
Interleukin-2 Receptor alpha Subunit physiology
Superantigens physiology
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 185
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21048104
- Full Text :
- https://doi.org/10.4049/jimmunol.1002416