Differential regulation of cytokine production by CD1d-restricted NKT cells in response to superantigen staphylococcal enterotoxin B exposure.
NKT cells are a heterogeneous population characterized by the ability to rapidly produce cytokines, such as interleukin 2 (IL-2), IL-4, and gamma interferon (IFN-gamma) in response to infections by viruses, bacteria, and parasites. The bacterial superantigen staphylococcal enterotoxin B (SEB) interacts with T cells bearing the Vbeta3, -7, or -8 T-cell receptors, inducing their expansion and cytokine secretion, leading to death in some cases due to cytokine poisoning. The majority of NKT cells bear the Vbeta7 or -8 T-cell receptor, suggesting that they may play a role in regulating this response. Using mice lacking NKT cells (CD1d(-/-) and Jalpha18(-/-) mice), we set out to identify the role of these cells in T-cell expansion, cytokine secretion, and toxicity induced by exposure to SEB. We find that Vbeta8(+) CD4(+) T-cell populations similarly expand in wild-type (WT) and NKT cell-null mice and that NKT cells did not regulate the secretion of IL-2. By contrast, these cells positively regulated the secretion of IL-4 and IFN-gamma production and negatively regulated the secretion of tumor necrosis factor alpha (TNF-alpha). However, this negative regulation of TNF-alpha secretion by NKT cells provides only a minor protective effect on SEB-mediated shock in WT mice compared to mice lacking NKT cells. These data suggest that NKT cells may regulate the nature of the cytokine response to exposure to the superantigen SEB and may act as regulatory T cells during exposure to this superantigen.
Ragin
Melanie J
MJ
Center for Molecular Immunology & Infectious Disease, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, 115 Henning Building, University Park, PA 16803, USA.
Sahu
Nisebita
N
August
Avery
A
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055610:Antigens, CD1d; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis*; D004768:Enterotoxins / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D018949:Antigens, CD1; D055610:Antigens, CD1d; D016207:Cytokines; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C031818:enterotoxin B, staphylococcal