scholarly journals Differential Regulation of Cytokine Production by CD1d-Restricted NKT Cells in Response to Superantigen Staphylococcal Enterotoxin B Exposure

2006 ◽  
Vol 74 (1) ◽  
pp. 282-288 ◽  
Author(s):  
Melanie J. Ragin ◽  
Nisebita Sahu ◽  
Avery August
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Nkt Cells ◽  
Staphylococcal Enterotoxin ◽  
Cytokine Secretion ◽  
Staphylococcal Enterotoxin B ◽  
Tnf Α ◽  
Ifn Γ ◽  
Enterotoxin B

ABSTRACT 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-γ) in response to infections by viruses, bacteria, and parasites. The bacterial superantigen staphylococcal enterotoxin B (SEB) interacts with T cells bearing the Vβ3, -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 Vβ7 or -8 T-cell receptor, suggesting that they may play a role in regulating this response. Using mice lacking NKT cells (CD1d−/− and Jα18−/− 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 Vβ8+ 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-γ production and negatively regulated the secretion of tumor necrosis factor alpha (TNF-α). However, this negative regulation of TNF-α 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.

scholarly journals Mycobacterium bovis BCG-Infected Mice Are More Susceptible to Staphylococcal Enterotoxin B-Mediated Toxic Shock than Uninfected Mice despite Reduced In Vitro Splenocyte Responses to Superantigens

2002 ◽  
Vol 70 (8) ◽  
pp. 4148-4157 ◽  
Author(s):  
João A. Pedras-Vasconcelos ◽  
Yvan Chapdelaine ◽  
Renu Dudani ◽  
Henk van Faassen ◽  
Dean K. Smith ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycobacterium Bovis ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Strong Type ◽  
Ifn Γ ◽  
Enterotoxin B

ABSTRACT Type 1 T-cell responses against intracellular pathogens play a crucial role in mediating protection. We examined whether the induction of a strong type 1 T-cell response during a chronic bacterial infection influences responses to superantigens capable of inducing acute shock. Intravenous infection of mice with Mycobacterium bovis BCG appeared to induce a progressive anergy towards staphylococcal enterotoxin B (SEB) and towards antigen preparation of BCG (BCG-Ag) itself, based on diminished gamma interferon (IFN-γ) production by SEB- and BCG-Ag-stimulated splenocytes from infected mice. In contrast to these in vitro results, injection of SEB into BCG-infected mice led to a dramatic increase in the serum IFN-γ levels and the death of infected but not of control mice. In vitro hyporesponsiveness towards SEB and BCG-Ag occurred only with unfractionated splenocyte cultures, as purified T cells from infected mice produced higher levels of IFN-γ. Hyporesponsiveness towards SEB and BCG-Ag in unfractionated splenocyte cultures was not due to suppressive antigen-presenting cells (APCs), as APCs from infected mice stimulated higher levels of IFN-γ from purified T cells. The diminished IFN-γ levels observed with bulk splenocytes appear to be due to changes in the T-cell-to-APC ratio that result in a decreased proportion of T cells, coupled to reduced proliferative responses and an increased susceptibility of effector T cells to activation-induced cell death in vitro. Our results indicate that the reported phenomena of T-cell anergy during mycobacterial infection may be an in vitro consequence of the development of a strong type 1 response in vivo.

scholarly journals In vivo induction of anergy in peripheral V beta 8+ T cells by staphylococcal enterotoxin B.

1990 ◽  
Vol 172 (4) ◽  
pp. 1091-1100 ◽  
Author(s):  
B L Rellahan ◽  
L A Jones ◽  
A M Kruisbeek ◽  
A M Fry ◽  
L A Matis
Keyword(s):  
T Cells ◽  
T Cell ◽  
No Reduction ◽  
Interleukin 2 ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Clonal Deletion ◽  
Enterotoxin B

We have developed a model of peripheral in vivo T cell tolerance that is induced by administration of the protein superantigen staphylococcal enterotoxin B (SEB). Rather than activating V beta 8+ T cells, in vivo administration of SEB induced in them a profound state of anergy. This was shown by their failure to proliferate to subsequent in vitro restimulation with SEB or to anti-V beta 8 antibodies. This unresponsiveness was V beta 8 specific since T cells from SEB-immunized mice responded normally to other antigens. 8 d after SEB administration, there was no reduction in the number of V beta 8+ T cells or in the intensity of V beta 8 T cell receptor (TCR) expression. Although a portion of the V beta 8+ T cells from SEB-primed mice were able to express interleukin 2 receptors (IL-2Rs), they failed to proliferate in response to exogenous IL-2, indicating they were defective in their IL-2 responsiveness. 2-4 wk after SEB administration, there was a reduction of approximately 50% in the number of V beta 8+ cells in immunized compared with control animals. There was, however, no reduction in the level of TCR expression on the remaining V beta 8+ cells. These data demonstrate that proteins that activate T cells in vitro in a V beta-specific manner can induce a state of anergy in peripheral T cells in vivo and may possibly further mediate clonal deletion in a portion of the tolerized cells.

scholarly journals Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice.

1996 ◽  
Vol 183 (6) ◽  
pp. 2481-2488 ◽  
Author(s):  
H W Mittrücker ◽  
A Shahinian ◽  
D Bouchard ◽  
T M Kündig ◽  
T W Mak
Keyword(s):  
T Cells ◽  
T Cell ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Rapid Induction ◽  
Cd28 Costimulation ◽  
Enterotoxin B ◽  
Deficient Mice

We used CD28-deficient mice to analyze the importance of CD28 costimulation for the response against Staphylococcal enterotoxin B (SEB) in vivo. CD28 was necessary for the strong expansion of V beta 8+ T cells, but not for deletion. The lack of expansion was not due to a failure of SEB to activate V beta 8+ T cells, as V beta 8+ T cells from both CD28-/- and CD28+/+ mice showed similar phenotypic changes within the first 24 h after SEB injection and cell cycle analysis showed that an equal percentage of V beta 8+ T cells started to proliferate. However, the phenotype and the state of proliferation of V beta 8+ T cells was different at later time points. Furthermore, in CD28-/- mice injection with SEB led to rapid induction of unresponsiveness in SEB responsive T cells, indicated by a drastic reduction of proliferation after secondary SEB stimulation in vitro. Unresponsiveness could also be demonstrated in vivo, as CD28-/- mice produced only marginal amounts of TNF alpha after rechallenge with SEB. In addition CD28-/- mice were protected against a lethal toxic shock induced by a second injection with SEB. Our results indicate that CD28 costimulation is crucial for the T cell-mediated toxicity of SEB and demonstrate that T cell stimulation in the absence of CD28 costimulation induces unresponsiveness in vivo.

scholarly journals Staphylococcal Enterotoxin B In Vivo Modulates both Gamma Interferon Receptor Expression and Ligand-Induced Activation of Signal Transducer and Activator of Transcription 1 in T Cells

2006 ◽  
Vol 75 (1) ◽  
pp. 306-313 ◽  
Author(s):  
R. Plaza ◽  
J. L. Rodriguez-Sanchez ◽  
C. Juarez
Keyword(s):  
T Cells ◽  
Gamma Interferon ◽  
Staphylococcal Enterotoxin ◽  
Receptor Expression ◽  
Protective Mechanism ◽  
Staphylococcal Enterotoxin B ◽  
Selective Blockade ◽  
Stat1 Signaling ◽  
Ifn Γ ◽  
Enterotoxin B

ABSTRACT Superantigens (SAg) are bacterial exotoxins that provoke extreme responses in the immune system; for example, the acute hyperactivation of SAg-reactive T cells that leads to toxic shock syndrome is followed within days by strong immunosuppression. The gamma interferon (IFN-γ) response is deeply affected in both extremes. The implication of IFN-γ in the pathophysiology of lethal shock induced in mice after a secondary challenge with the SAg staphylococcal enterotoxin B (SEB) prompted us to study the regulation of IFN-γ secretion and the intracellular response. We demonstrate in this study that a rechallenge with SEB becomes lethal only when given inside a critical time window after SEB priming and is associated with an increase of IFN-γ serum release 72 h after priming. However, at this time, a selective blockade of IFN-γ/STAT1 signaling develops in spleen cells, correlating with a lack of expression of the IFN-γ receptor beta subunit and STAT1 in the T-cell population. Selective blockade of the STAT1 signaling pathway—while simultaneously maintaining STAT3 signaling and expression—may be a protective mechanism that shortens IFN-γ production during the Th1 effector response. This blockade may also have consequences on switching towards a suppressor phenotype with chronic exposure to the superantigen.

scholarly journals The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells.

1990 ◽  
Vol 171 (2) ◽  
pp. 455-464 ◽  
Author(s):  
P Marrack ◽  
M Blackman ◽  
E Kushnir ◽  
J Kappler
Keyword(s):  
Weight Loss ◽  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cell Function ◽  
Class Ii ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Rapid Weight Loss ◽  
Enterotoxin B

Staphylococcal enterotoxin B (SEB) has been shown in the past to be a potent T cell stimulant in mouse or man. The toxin acts as a superantigen that is, it binds to class II MHC proteins and, as such a complex, stimulates T cells bearing particular V beta s as part of their receptors. The toxin also has several pathological effects, causing, in mice, rapid weight loss, thymus atrophy, immunosuppression, and, at high doses, death. The data in this paper show that at least one of these effects, weight loss, is T cell mediated. Staphylococcal enterotoxin-mediated weight loss is MHC dependent, and is almost absent in animals expressing MHC class II molecules, which, complexed with SEB, are poor T cell stimulants. Also, mice that lack T cell function, genetically or because of cyclosporin A treatment, lose no or less weight than controls in response to SEB. Finally, animals bred such that they express few T cells bearing V beta s with which SEB can interact lose much less weight in response to the toxin than littermate controls that have higher numbers of reactive T cells. It is therefore suggested that the pathological effects of the staphylococcal, T cell-stimulating toxins in mouse and man may be partially or wholly the consequence of massive T cell stimulation.

scholarly journals Endogenous Superantigens Shape Response to Exogenous Superantigens

2005 ◽  
Vol 12 (9) ◽  
pp. 1119-1122 ◽  
Author(s):  
Govindarajan Rajagopalan ◽  
Manisha Singh ◽  
Moon M. Sen ◽  
Narayana S. Murali ◽  
Karl A. Nath ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Negative Selection ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Enterotoxin B

ABSTRACT Endogenous superantigen-mediated thymic negative selection resulted in a paucity of mature T cells bearing T-cell receptor (TCR) Vβ8 in the periphery. Consequently, the magnitude of immune response to exogenous superantigen staphylococcal enterotoxin B, which activates TCR Vβ8+ T cells, was significantly reduced and conferred protection from superantigen-induced mortality.

scholarly journals Staphylococcal enterotoxin B‐induced T‐cell anergy is mediated by regulatory T cells

Immunology ◽  
1998 ◽  
Vol 94 (3) ◽  
pp. 331-339 ◽  
Author(s):  
Z.‐Q. WANG ◽  
T. ORLIKOWSKY ◽  
A. DUDHANE ◽  
V. TREJO ◽  
G. E. DANNECKER ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
T Cell Anergy ◽  
Enterotoxin B ◽  
Cell Anergy

Suppression of cytolytic T-cell activity by staphylococcal enterotoxin B-induced suppressor cells: Role of interleukin 2

1986 ◽  
Vol 103 (1) ◽  
pp. 147-159 ◽  
Author(s):  
Yee-Shin Lin ◽  
Mahadev R. Patel ◽  
T.Juhani Linna ◽  
Thomas J. Rogers
Keyword(s):  
T Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Enterotoxin B

scholarly journals Differentiation of Antigen-Specific T Cells with Limited Functional Capacity during Mycobacterium tuberculosis Infection

2013 ◽  
Vol 82 (1) ◽  
pp. 132-139 ◽  
Author(s):  
Yun Hee Jeong ◽  
Bo-Young Jeon ◽  
Sun-Hwa Gu ◽  
Sang-Nae Cho ◽  
Sung Jae Shin ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Memory T Cells ◽  
Interleukin 2 ◽  
Effector Memory ◽  
Memory Cells ◽  
Content Type ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACTDespite the generation ofMycobacterium tuberculosis-specific T cell immune responses during the course of infection, only 5 to 10% of exposed individuals develop active disease, while others develop a latent infection. This phenomenon suggests defectiveM. tuberculosis-specific immunity, which necessitates more careful characterization ofM. tuberculosis-specific T cell responses. Here, we longitudinally analyzed the phenotypes and functions ofM. tuberculosis-specific T cells. In contrast to the functional exhaustion of T cells observed after chronic infection,M. tuberculosis-specific CD8+T cells differentiated into either effector (CD127loCD62Llo) or effector memory (CD127hiCD62Llo) cells, but not central memory cells (CD127hiCD62Lhi), with low programmed death 1 (PD-1) expression, even in the presence of high levels of bacteria. Additionally,M. tuberculosis-specific CD8+and CD4+T cells produced substantial levels of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), but not interleukin 2 (IL-2), uponin vitrorestimulation. AmongM. tuberculosis-specific CD8+T cells, CD127hieffector memory cells displayed slower ongoing turnover but greater survival potential. In addition, these cells produced more IFN-γ and TNF-α and displayed lytic activity upon antigen stimulation. However, the effector function ofM. tuberculosis-specific CD8+CD127hieffector memory T cells was inferior to that of canonical CD8+CD127himemory T cells generated after acute lymphocytic choriomeningitis virus infection. Collectively, our data demonstrate thatM. tuberculosis-specific T cells can differentiate into memory T cells during the course ofM. tuberculosisinfection independent of the bacterial burden but with limited functionality. These results provide a framework for further understanding the mechanisms ofM. tuberculosisinfection that can be used to develop more effective vaccines.

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