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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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Anergy of enriched CD4+ T cells from SEA-treated transgenic mice. Tg CD4+ cells were broadly unresponsive to antigenic restimulation in vitro after in vivo exposure to SEA. [3H]thymidine incorporation  by CD4+ T cells stimulated with (a) 5 μM PCCF and APCs, (b) increasing  concentrations of PCCF and APCs, and (c) other T cell mitogens. (d) Cytokine production by CD4+ T cells was also decreased by the in vivo SEA  treatment. Similar results were seen in at least three repeated experiments.
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Figure 1: Anergy of enriched CD4+ T cells from SEA-treated transgenic mice. Tg CD4+ cells were broadly unresponsive to antigenic restimulation in vitro after in vivo exposure to SEA. [3H]thymidine incorporation by CD4+ T cells stimulated with (a) 5 μM PCCF and APCs, (b) increasing concentrations of PCCF and APCs, and (c) other T cell mitogens. (d) Cytokine production by CD4+ T cells was also decreased by the in vivo SEA treatment. Similar results were seen in at least three repeated experiments.

Mentions: To verify that SEA induces anergy in Tg CD4+ cells, AND mice were injected with 20 μg of SEA (intravenously). 6–8 d later, splenic CD4+ cells were enriched using Ab to CD8, class II MHC, and heat stable antigen to deplete CD8+ T and B cells. DNA synthesis and cytokine production were used to assess the effect of the SAg treatment. In a typical experiment, the enriched CD4+ cells from SEA-treated, but not control, mice failed to synthesize DNA over a wide range of cell numbers (Fig. 1 a) and PCCF doses (Fig. 1 b). Even ionomycin (Ca2+ ionophore) and PMA, which together circumvent the need for TCR signaling, elicited little response from the SEA-treated cells as compared to the untreated control cells (Fig. 1 c).


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)

Anergy of enriched CD4+ T cells from SEA-treated transgenic mice. Tg CD4+ cells were broadly unresponsive to antigenic restimulation in vitro after in vivo exposure to SEA. [3H]thymidine incorporation  by CD4+ T cells stimulated with (a) 5 μM PCCF and APCs, (b) increasing  concentrations of PCCF and APCs, and (c) other T cell mitogens. (d) Cytokine production by CD4+ T cells was also decreased by the in vivo SEA  treatment. Similar results were seen in at least three repeated experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Anergy of enriched CD4+ T cells from SEA-treated transgenic mice. Tg CD4+ cells were broadly unresponsive to antigenic restimulation in vitro after in vivo exposure to SEA. [3H]thymidine incorporation by CD4+ T cells stimulated with (a) 5 μM PCCF and APCs, (b) increasing concentrations of PCCF and APCs, and (c) other T cell mitogens. (d) Cytokine production by CD4+ T cells was also decreased by the in vivo SEA treatment. Similar results were seen in at least three repeated experiments.
Mentions: To verify that SEA induces anergy in Tg CD4+ cells, AND mice were injected with 20 μg of SEA (intravenously). 6–8 d later, splenic CD4+ cells were enriched using Ab to CD8, class II MHC, and heat stable antigen to deplete CD8+ T and B cells. DNA synthesis and cytokine production were used to assess the effect of the SAg treatment. In a typical experiment, the enriched CD4+ cells from SEA-treated, but not control, mice failed to synthesize DNA over a wide range of cell numbers (Fig. 1 a) and PCCF doses (Fig. 1 b). Even ionomycin (Ca2+ ionophore) and PMA, which together circumvent the need for TCR signaling, elicited little response from the SEA-treated cells as compared to the untreated control cells (Fig. 1 c).

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