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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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(a) Purity of CD4+ cells after enrichment with Ab and C′  (left) and positive selection on magnetic columns (right). (b) Number of  live CD4+ cells recovered on day 4.
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Figure 3: (a) Purity of CD4+ cells after enrichment with Ab and C′ (left) and positive selection on magnetic columns (right). (b) Number of live CD4+ cells recovered on day 4.

Mentions: Extensive purification procedures were used to determine whether the anergic CD4+ cells were intrinsically unresponsive or, alternatively, were being influenced by other cells or factors from the injected mice such as those responsible for the trans suppression. Positive selection using magnetic bead columns was used to generate pure populations of CD4+ cells with <1–5% contaminating non-CD4+ cells from both control and SEA treated mice (Fig. 3 a).


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)

(a) Purity of CD4+ cells after enrichment with Ab and C′  (left) and positive selection on magnetic columns (right). (b) Number of  live CD4+ cells recovered on day 4.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: (a) Purity of CD4+ cells after enrichment with Ab and C′ (left) and positive selection on magnetic columns (right). (b) Number of live CD4+ cells recovered on day 4.
Mentions: Extensive purification procedures were used to determine whether the anergic CD4+ cells were intrinsically unresponsive or, alternatively, were being influenced by other cells or factors from the injected mice such as those responsible for the trans suppression. Positive selection using magnetic bead columns was used to generate pure populations of CD4+ cells with <1–5% contaminating non-CD4+ cells from both control and SEA treated mice (Fig. 3 a).

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