Immunological adjuvants promote activated T cell survival via induction of Bcl-3

Abstract

Injection of soluble protein antigen into animals causes abortive proliferation of the responding T cells. Immunological adjuvants boost T cell responses at least in part by increasing the survival of activated T cells during and after the initial proliferative phase of their clonal expansion. To understand how adjuvants promote T cell survival, we used gene microarrays to analyze gene expression in T cells activated either with antigen alone or in the presence of two different adjuvants. Among the genes whose expression was increased by both adjuvants was the IκB family member Bcl-3. Retroviral infection experiments showed that expression of Bcl-3 increased survival of activated T cells in vitro and in vivo. Adjuvants may therefore improve survival of activated T cells via induction of Bcl-3.

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Figure 1: RNA transcripts of the genes encoding Bcl-3 and RelB are increased in T cells exposed to adjuvant.
Figure 2: Survival of activated T cells can be measured with Thy1.1+ retroviral vectors.
Figure 3: Bcl-3 increased survival of activated T cells.
Figure 4: Bcl-3 did not affect T cell proliferation.
Figure 5: Bcl-3 increased activated T cell survival in vivo.

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Acknowledgements

We thank B. Townend and S. Sobus for help with the cell sorting and flow cytometry and S. Madden and C. Slaughter for Affymetrix GeneChip analysis. Supported by USPHS grants AI-17134, AI-18785 and AI-22295.

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Correspondence to Philippa Marrack.

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