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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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Apoptosis of CD4+ T cells from SEA-treated Tg mice. TdT  staining revealed DNA fragmentation in the CD4+ T cells from SEA-treated mice. SEA-treated animals were analyzed 2 and 4 d after SEA injection (two animals each), immediately ex vivo, and 12 h after antigenic  restimulation with APCs and PCCF. TdT staining of gated CD4+ T cell  populations are shown.
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Figure 8: Apoptosis of CD4+ T cells from SEA-treated Tg mice. TdT staining revealed DNA fragmentation in the CD4+ T cells from SEA-treated mice. SEA-treated animals were analyzed 2 and 4 d after SEA injection (two animals each), immediately ex vivo, and 12 h after antigenic restimulation with APCs and PCCF. TdT staining of gated CD4+ T cell populations are shown.

Mentions: Since much peripheral T cell death is mediated by Fas–FasL interactions (43), we investigated the potential contribution of Fas-mediated suicide to the anergy of the CD4+ cells in our model. To do this we directly analyzed enriched CD4+ cells from SEA-treated AND mice for evidence of intracellular DNA damage (44) by TUNEL staining. CD4+ cells were isolated from the spleens of untreated control (no SEA) and injected mice, 2 and 4 d after SEA treatment (two mice each). The enriched cells were either restimulated in vitro with APC, PCCF, and rIL-2 for 12 h, or analyzed immediately (ex vivo) for DNA damage (Fig. 8). Gated populations of CD4+ cells are shown.


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)

Apoptosis of CD4+ T cells from SEA-treated Tg mice. TdT  staining revealed DNA fragmentation in the CD4+ T cells from SEA-treated mice. SEA-treated animals were analyzed 2 and 4 d after SEA injection (two animals each), immediately ex vivo, and 12 h after antigenic  restimulation with APCs and PCCF. TdT staining of gated CD4+ T cell  populations are shown.
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Related In: Results  -  Collection

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Figure 8: Apoptosis of CD4+ T cells from SEA-treated Tg mice. TdT staining revealed DNA fragmentation in the CD4+ T cells from SEA-treated mice. SEA-treated animals were analyzed 2 and 4 d after SEA injection (two animals each), immediately ex vivo, and 12 h after antigenic restimulation with APCs and PCCF. TdT staining of gated CD4+ T cell populations are shown.
Mentions: Since much peripheral T cell death is mediated by Fas–FasL interactions (43), we investigated the potential contribution of Fas-mediated suicide to the anergy of the CD4+ cells in our model. To do this we directly analyzed enriched CD4+ cells from SEA-treated AND mice for evidence of intracellular DNA damage (44) by TUNEL staining. CD4+ cells were isolated from the spleens of untreated control (no SEA) and injected mice, 2 and 4 d after SEA treatment (two mice each). The enriched cells were either restimulated in vitro with APC, PCCF, and rIL-2 for 12 h, or analyzed immediately (ex vivo) for DNA damage (Fig. 8). Gated populations of CD4+ cells are shown.

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