Transferable anergy: superantigen treatment induces CD4+ T cell tolerance that is reversible and requires CD4-CD8- cells and interferon gamma.
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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.
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Affiliation: Trudeau Institute, Saranac Lake, New York 12983, USA.
ABSTRACT
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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. Related in: MedlinePlus |
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Figure 2: Cells from SEA-treated mice suppress control CD4+ T cell responses. (a) Purity of cells after purification with Ab and C′. (b) Anergic cells from SEA-treated mice inhibited effector generation by normal CD4+ T cells in mixed wells. (c) Non-CD4+ cells from SEA-treated mice were sufficient for the suppression to be transferred between in vitro cultures. Live CD4+ T cell recovery on day 4 is shown. Mentions: In non-Tg models, only a fraction of the T cells respond to SAg and the response is heterogeneous even for a single Vβ. Consequently, anergic cells have rarely been isolated and the possibility that unresponsiveness is maintained by a suppresser mechanism has not been adequately addressed. To test for such a suppresser mechanism in the AND mouse model, we added enriched CD4+ cells from the SEA-treated mice to control CD4+ cells in mixed cultures (Fig. 2). Since DNA synthesis is a precursor of cell division, but may not always correlate with proliferation if cells undergo apoptosis, live cell recoveries were used to measure the extent of the CD4+ cell response. |
View Article: PubMed Central - PubMed
Affiliation: Trudeau Institute, Saranac Lake, New York 12983, USA.