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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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Cytokine production was restored by purification.  SEA-treated and control CD4+  T cells were purified by sterile  FACS® sorting or enriched with  Ab and C′ and stimulated at 106  cells/ml with anti-CD3 and  -CD28. Supernatants were analyzed 24 h after restimulation using ELISA assays and proliferation assays with NK.3 cells.
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Figure 5: Cytokine production was restored by purification. SEA-treated and control CD4+ T cells were purified by sterile FACS® sorting or enriched with Ab and C′ and stimulated at 106 cells/ml with anti-CD3 and -CD28. Supernatants were analyzed 24 h after restimulation using ELISA assays and proliferation assays with NK.3 cells.

Mentions: We used sterile FACS® sorting to determine whether cytokine production was restored by purification. Sorted CD4+ cells were stimulated and analyzed for the ability to synthesize cytokine mRNA (Fig. 4). 24 h supernatants were also analyzed for cytokine content (Fig. 5).


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)

Cytokine production was restored by purification.  SEA-treated and control CD4+  T cells were purified by sterile  FACS® sorting or enriched with  Ab and C′ and stimulated at 106  cells/ml with anti-CD3 and  -CD28. Supernatants were analyzed 24 h after restimulation using ELISA assays and proliferation assays with NK.3 cells.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Cytokine production was restored by purification. SEA-treated and control CD4+ T cells were purified by sterile FACS® sorting or enriched with Ab and C′ and stimulated at 106 cells/ml with anti-CD3 and -CD28. Supernatants were analyzed 24 h after restimulation using ELISA assays and proliferation assays with NK.3 cells.
Mentions: We used sterile FACS® sorting to determine whether cytokine production was restored by purification. Sorted CD4+ cells were stimulated and analyzed for the ability to synthesize cytokine mRNA (Fig. 4). 24 h supernatants were also analyzed for cytokine content (Fig. 5).

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