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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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Related in: MedlinePlus

Fas-mediated death  is not required for transferable  anergy. Effector cell generation  by Fas-deficient CD4+ T cells  from C3H.MRL-lpr/lpr mice (b)  and syngeneic controls (a) was  suppressed by splenocytes from  SEA-treated AND mice in  mixed cultures and could be restored by anti–IFN-γ Ab. The  number of live CD4+ T cells recovered on day 4 is shown.
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Figure 9: Fas-mediated death is not required for transferable anergy. Effector cell generation by Fas-deficient CD4+ T cells from C3H.MRL-lpr/lpr mice (b) and syngeneic controls (a) was suppressed by splenocytes from SEA-treated AND mice in mixed cultures and could be restored by anti–IFN-γ Ab. The number of live CD4+ T cells recovered on day 4 is shown.

Mentions: To determine whether Fas–FasL interactions were mediating cell death in the suppressed cultures, we compared Fas-deficient CD4+ cells from MRL-lpr/lpr mice (45) with cells from syngeneic wild-type mice, as targets of the SEA-mediated suppression in the transferable anergy model. Enriched CD4−CD8− cells from SEA-treated AND mice were mixed with Fas-deficient CD4+ cells from untreated MRL-lpr/lpr mice (Fas−) or Fas-bearing (Fas+) cells from wild-type controls (Fig. 9) and stimulated with APC, Con A, and rIL-2. In both cases, the SEA-treated lymphocytes suppressed the recovery of live CD4+ cells (Fas+ and Fas−) from untreated animals (Fig. 9, a and b, respectively). Both cell recoveries were also substantially increased by the addition of anti–IFN-γ Ab to the mixed wells. Thus, CD4+ cells that lacked a functional Fas antigen could be suppressed by the SEA-treated cells from AND mice by an IFN-γ–dependent mechanism, demonstrating that at least some of the anergy was not mediated via Fas–FasL.


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)

Fas-mediated death  is not required for transferable  anergy. Effector cell generation  by Fas-deficient CD4+ T cells  from C3H.MRL-lpr/lpr mice (b)  and syngeneic controls (a) was  suppressed by splenocytes from  SEA-treated AND mice in  mixed cultures and could be restored by anti–IFN-γ Ab. The  number of live CD4+ T cells recovered on day 4 is shown.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: Fas-mediated death is not required for transferable anergy. Effector cell generation by Fas-deficient CD4+ T cells from C3H.MRL-lpr/lpr mice (b) and syngeneic controls (a) was suppressed by splenocytes from SEA-treated AND mice in mixed cultures and could be restored by anti–IFN-γ Ab. The number of live CD4+ T cells recovered on day 4 is shown.
Mentions: To determine whether Fas–FasL interactions were mediating cell death in the suppressed cultures, we compared Fas-deficient CD4+ cells from MRL-lpr/lpr mice (45) with cells from syngeneic wild-type mice, as targets of the SEA-mediated suppression in the transferable anergy model. Enriched CD4−CD8− cells from SEA-treated AND mice were mixed with Fas-deficient CD4+ cells from untreated MRL-lpr/lpr mice (Fas−) or Fas-bearing (Fas+) cells from wild-type controls (Fig. 9) and stimulated with APC, Con A, and rIL-2. In both cases, the SEA-treated lymphocytes suppressed the recovery of live CD4+ cells (Fas+ and Fas−) from untreated animals (Fig. 9, a and b, respectively). Both cell recoveries were also substantially increased by the addition of anti–IFN-γ Ab to the mixed wells. Thus, CD4+ cells that lacked a functional Fas antigen could be suppressed by the SEA-treated cells from AND mice by an IFN-γ–dependent mechanism, demonstrating that at least some of the anergy was not mediated via Fas–FasL.

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