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Transferable anergy: superantigen treatment induces CD4+ T cell tolerance that is reversible and requires CD4-CD8- cells and interferon gamma.

Cauley LS, Cauley KA, Shub F, Huston G, Swain SL - J. Exp. Med. (1997)

Bottom Line: Bacterial superantigens induce peripheral unresponsiveness in CD4+ T cell populations that express appropriate Vbeta chains.However, when the SEA-treated CD4+ cells were completely purified away from all other contaminating cells, they regained the ability to proliferate and secrete cytokines.Further analysis demonstrated that interferon gamma, but not the Fas receptor, played a critical role in the suppression.

View Article: PubMed Central - PubMed

Affiliation: Trudeau Institute, Saranac Lake, New York 12983, USA.

ABSTRACT
Bacterial superantigens induce peripheral unresponsiveness in CD4+ T cell populations that express appropriate Vbeta chains. We have used Vbeta3/Valpha11 T cell receptor transgenic (Tg) mice and the Vbeta3-specific superantigen staphylococcal enterotoxin A (SEA) to further investigate the mechanisms that contribute to such unresponsiveness. As in other models, in vivo exposure to SEA rendered the Tg CD4+ cells unresponsive to subsequent restimulation in vitro with antigen or mitogens. However, when the SEA-treated CD4+ cells were completely purified away from all other contaminating cells, they regained the ability to proliferate and secrete cytokines. Moreover, enriched CD4-CD8- cells from the SEA-treated mice suppressed the responses of fresh control CD4+ cells in mixed cultures indicating that the apparent "anergy" was both transferable and reversible. Further analysis demonstrated that interferon gamma, but not the Fas receptor, played a critical role in the suppression.

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Anti–IFN-γ reverses  the transferable suppression by  cells from SEA-treated mice. (a)  Mixed cultures of anergic and  control CD4+ T cells were stimulated with APCs and PCCF in  the presence and absence of the  neutralizing XMG1.2 Ab. Live  CD4+ cell recovery on day 4 is  shown. (b) CD4+ effector cells  generated in the presence of the XMG1.2 Ab develop the ability to secrete cytokines after antigenic restimulation. Effector cells were further  purified on magnetic bead columns and restimulated with PCCF and  APC. (c) 24-h supernatants were analyzed for cytokine content.
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Figure 7: Anti–IFN-γ reverses the transferable suppression by cells from SEA-treated mice. (a) Mixed cultures of anergic and control CD4+ T cells were stimulated with APCs and PCCF in the presence and absence of the neutralizing XMG1.2 Ab. Live CD4+ cell recovery on day 4 is shown. (b) CD4+ effector cells generated in the presence of the XMG1.2 Ab develop the ability to secrete cytokines after antigenic restimulation. Effector cells were further purified on magnetic bead columns and restimulated with PCCF and APC. (c) 24-h supernatants were analyzed for cytokine content.

Mentions: To investigate whether IFN-γ played a similar role in the transferable suppression, we added anti–IFN-γ to mixed cultures of control CD4+ cells with enriched CD4−CD8− cells from SEA-treated mice (Fig. 7 a). As expected, the cells from the SEA-treated mice suppressed the recovery of fresh CD4+ cells by 20-fold when mixed at a ratio of 1:1 (Fig. 2). The addition of anti–IFN-γ to the mixed cultures restored the recovery of these cells to the levels seen when no SEA-treated cells were added.


Transferable anergy: superantigen treatment induces CD4+ T cell tolerance that is reversible and requires CD4-CD8- cells and interferon gamma.

Cauley LS, Cauley KA, Shub F, Huston G, Swain SL - J. Exp. Med. (1997)

Anti–IFN-γ reverses  the transferable suppression by  cells from SEA-treated mice. (a)  Mixed cultures of anergic and  control CD4+ T cells were stimulated with APCs and PCCF in  the presence and absence of the  neutralizing XMG1.2 Ab. Live  CD4+ cell recovery on day 4 is  shown. (b) CD4+ effector cells  generated in the presence of the XMG1.2 Ab develop the ability to secrete cytokines after antigenic restimulation. Effector cells were further  purified on magnetic bead columns and restimulated with PCCF and  APC. (c) 24-h supernatants were analyzed for cytokine content.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198967&req=5

Figure 7: Anti–IFN-γ reverses the transferable suppression by cells from SEA-treated mice. (a) Mixed cultures of anergic and control CD4+ T cells were stimulated with APCs and PCCF in the presence and absence of the neutralizing XMG1.2 Ab. Live CD4+ cell recovery on day 4 is shown. (b) CD4+ effector cells generated in the presence of the XMG1.2 Ab develop the ability to secrete cytokines after antigenic restimulation. Effector cells were further purified on magnetic bead columns and restimulated with PCCF and APC. (c) 24-h supernatants were analyzed for cytokine content.
Mentions: To investigate whether IFN-γ played a similar role in the transferable suppression, we added anti–IFN-γ to mixed cultures of control CD4+ cells with enriched CD4−CD8− cells from SEA-treated mice (Fig. 7 a). As expected, the cells from the SEA-treated mice suppressed the recovery of fresh CD4+ cells by 20-fold when mixed at a ratio of 1:1 (Fig. 2). The addition of anti–IFN-γ to the mixed cultures restored the recovery of these cells to the levels seen when no SEA-treated cells were added.

Bottom Line: Bacterial superantigens induce peripheral unresponsiveness in CD4+ T cell populations that express appropriate Vbeta chains.However, when the SEA-treated CD4+ cells were completely purified away from all other contaminating cells, they regained the ability to proliferate and secrete cytokines.Further analysis demonstrated that interferon gamma, but not the Fas receptor, played a critical role in the suppression.

View Article: PubMed Central - PubMed

Affiliation: Trudeau Institute, Saranac Lake, New York 12983, USA.

ABSTRACT
Bacterial superantigens induce peripheral unresponsiveness in CD4+ T cell populations that express appropriate Vbeta chains. We have used Vbeta3/Valpha11 T cell receptor transgenic (Tg) mice and the Vbeta3-specific superantigen staphylococcal enterotoxin A (SEA) to further investigate the mechanisms that contribute to such unresponsiveness. As in other models, in vivo exposure to SEA rendered the Tg CD4+ cells unresponsive to subsequent restimulation in vitro with antigen or mitogens. However, when the SEA-treated CD4+ cells were completely purified away from all other contaminating cells, they regained the ability to proliferate and secrete cytokines. Moreover, enriched CD4-CD8- cells from the SEA-treated mice suppressed the responses of fresh control CD4+ cells in mixed cultures indicating that the apparent "anergy" was both transferable and reversible. Further analysis demonstrated that interferon gamma, but not the Fas receptor, played a critical role in the suppression.

Show MeSH
Related in: MedlinePlus