Differential induction of interferon gamma gene expression after activation of CD4+ T cells by conventional antigen and Mls superantigen.

Patarca, Roberto; Wei, Feng-Yi; Iregui, Maria Victoria; Cantor, Harvey

doi:10.1073/pnas.88.7.2736

Cited by 26 publications

(10 citation statements)

References 35 publications

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“…Further studies should clarify these issues. Nevertheless, the observations that a conventional antigen and a superantigen induce different cytokine gene expressions in the same T-cell clone (24) and that antigen and superantigen induce additive responses (20) support the theory that intracellular biochemical events initiated by TCR ligation by these two classes of ligands are functionally distinct.…”

Section: Discussionmentioning

confidence: 92%

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

Oyaizu

Chirmule

Yagura

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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The role of the CD4 molecule in activation of T-helper cells was examined by investigating the effect of an anti-CD4 monoclonal antibody (Leu3a) in conventional peptide antigen-specific cloned T-helper cells that are also reactive to staphylococcal enterotoxin B (SEB). These T-helper cell clones are CD4+/CD45RO+/T-cell antigen receptor «-chain variable region 12-positive and can respond to nominal peptide antigens and SEB by proliferation in the presence of class II major histocompatibility complex-expressing accessory cells. Although antigen and SEB were comparable in their ability to induce proliferative responses, interleukin 2 (IL-2) production, and IL-2 receptor a-chain expression, stimulatin with SEB failed to trigger phosphatidylinositol hydrolysis or a rise in the intracellular free calcium ion concentration. Leu3a treatment inhibited antigen-induced proliferative responses of T cells with concomitant suppression of IL-2 production and IL-2 receptor expression. In contrast, SEB-induced responses were unaffected by Leu3a. These findings indicate that the functional consequences of binding (ligation) of conventional antigen and of superantigen with the T-cell receptor are distinct in the context of both signal transduction pathways and participation of CD4 molecules.Superantigens are molecules that are recognized differently from conventional antigens by responsive T cells. Superantigens are characterized by their ability to bind to a component or components of class II major histocompatibility complex (MHC) molecules and to stimulate T cells in a ,B3chain variable region (V9)-specific manner (1). Conventional antigens bind within a polymorphic groove on class II MHC molecules and interact only with T cells bearing unique a and ,B T-cell antigen receptors (TCRs). Superantigens interact with class II molecules outside the antigen groove (2) and stimulate distinct Vg-expressing T cells (1 Cells. Antigen-specific human T-cell clones specific for tetanus toxoid and for purified protein derivative (PPD) were developed as described (7). The clones used, PPD3.2, PPD3.5, and Tt4.2, express the phenotype CD3+/CD4+/ CD45RO+ (UCHL1+). These clones also react with mAb to V,12 (T Cell Science, Cambridge, MA). They proliferate and secrete IL-2 after stimulation with antigen in the presence of irradiated autologous Epstein-Barr virus-transformed B cells as antigen-presenting cells (APC), designated EBV300 for clones PPD3.2 and PPD3.5 and EBV400 for Tt4.

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Section: Discussionmentioning

confidence: 92%

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

Oyaizu

Chirmule

Yagura

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…Surprisingly, the VB8-specific antibody F23.1 was not capable of killing GAIN-or RU-38486-sensitized BALB/c mice (Table 1), indicating that the mode of stimulation exerted by this antibody must differ from that of the equally V~8-specific superantigen SEB. Accordingly, the signal transduction cascades triggered by superantigens and conventional stimuli exhibit an only partial overlap in vitro (26,27). Moreover, F23.1 differs from SEB in the sense that its in vitro application fails to trigger an expansion of V/% + T cells but rather provokes an immediate programmed cell death-mediated depletion of V/38 + T cells (data not shown).…”

Section: Endogenous Gc Protect Mice Against the Lethal Effect Of Acutmentioning

confidence: 99%

Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo.

Gonzalo

González–García

Martı́nez

et al. 1993

The Journal of Experimental Medicine

162

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SummaryPoly-and oligodonal T cell stimuli like anti-CD3e monoclonal antibody or Staphylococcus aureus enterotoxin B (SEB), injected at doses that per se are not lethal, provoke acute death within less than 24 h, provided that endogenous glucocorticoids (GC) are depleted by adrenalectomy or by injection of saturating amounts of the GC receptor antagonist RU-38486 (mifepristone). Pharmacological doses of the GC agonist dexamethasone (DEX) alter the in vivo response of splenic V38 + T cells to SEB, thus impeding the expansion of such cells and causing their rapid (3 d) clonal deletion. In contrast, coadministration of RU-38486 counteracts a SEB-induced early (12 h) reduction of V38+CD4 + and V38+CD8 + spleen cells. In vivo T cell stimulation by injection of bacterial superantigen induces a rapid (peak at 90-120 rain) increase in corticosterone serum levels, suggesting that endogenous GC might control early T cell activation. Accordingly, kinetic studies revealed that RU-38486 has to be administered within 2 h after superantigen administration to exert its lethal effect. Similarly, exogenous GC must be injected during this critical phase (2 h) to rescue animals from acute death induced by coinjection of SEB and D-galactosamine (GAIN). Adrenalectomy, injection of RU-38486 and priming with GaIN per se provoke the programmed death of peripheral CD4 + and CD8 + T cells. Thus, three manipulations that sensitize mice for the lethal effect of T cell stimulation also exert a proapoptotic effect on peripheral T cells. In synthesis, endogenous and exogenous GC regulate T cell responses and determine the propensity of peripheral T cells to undergo apoptosis. SYnthetic glucocorticoid (GC) 1 agonists are used for therapy of a broad spectrum of organ-specific and generalized autoimmune diseases. In the same way, endogenous GC secreted by the adrenal glands may act as immunosuppressive and antiinflammatory agents that contend lifethreatening overreactions of the immune system, as well as autoaggressive responses (for reviews see references 1, 2). GC inhibit macrophage functions, including cytotoxic functions, processing, and presentation of antigen to T cells, inhibit the production of IL-2 and IFN-3, in T lymphocytes (3), shift T cell responses from the Thl to the Th2 type (4), decrease the activity of NK cells, induce programmed cell death in a variety of different immunologically relevant cells, including immature T and B cell precursors (for reviews see references 5, 6) and mature T cells (7), and inhibit the synthesis of a variety of proimflammatory cytokines (IL-1, IL-6, and TNF-o 0 (8). Immune activation frequently is associated with an in- crease in ACTH and GC secretion, and the susceptibility of certain animal strains to develop autoimmune diseases is linked to a deficient GC-mediated inhibition of immune function (2, 9-12).Recently, a synthetic steroid, KU-38486 (RU486, mifepristone), with potent antiprogestational and antiglucocorticoid activity has become available for clinical use as an abortifacient agent (13,14) an...

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“…Recent studies have suggested that superantigens interact with MHC class II molecules outside the antigen-binding groove (8) and may bind to the T-cell receptor (TCR) away from the predicted combining site for conventional ligands (9). These findings have raised the possibility that the interaction of the TCR with conventional peptide antigen and with superantigen may have distinct functional consequences (10). We have addressed this question using murine T helper (TH) clones that bear receptors that allow clonal proliferation in response to both classes of ligand.…”

mentioning

confidence: 99%

Conventional antigen and superantigen may be coupled to distinct and cooperative T-cell activation pathways.

Liu

Lampe²,

Iregui³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Differential induction of interferon gamma gene expression after activation of CD4+ T cells by conventional antigen and Mls superantigen.

Cited by 26 publications

References 35 publications

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo.

Conventional antigen and superantigen may be coupled to distinct and cooperative T-cell activation pathways.

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