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Transcriptional regulator Id2 mediates CD8+ T cell immunity

Nature Immunology volume 7, pages 1317–1325 (2006)Cite this article

Abstract

Transcriptional programs that initiate and sustain the proliferation, differentiation and survival of CD8+ T cells during immune responses are not completely understood. Here we show that inhibitor of DNA binding 2 (Id2), an antagonist of E protein transcription factors, was upregulated in CD8+ T cells during infection and that expression of Id2 was maintained in memory CD8+ T cells. Although Id2-deficient naive CD8+ T cells recognized antigen and proliferated normally early after infection, effector CD8+ T cells did not accumulate because the cells were highly susceptible to apoptosis. Id2-deficient CD8+ T cells responding to infection had changes in the expression of genes that influence survival and had altered memory formation. Our data emphasize the importance of Id2 in regulating gene expression by CD8+ T cells and the magnitude of effector responses, suggesting a mechanism involving Id protein– and E protein–mediated survival and differentiation of mature T cells.

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Figure 1: Id2 is upregulated during the in vivo CD8+ T cell response to infection.
Figure 2: Id2 deficiency leads to a loss of CD8+ memory T cell subsets.
Figure 3: Defective response to listeria infection by Id2-deficient CD8+ T cells.
Figure 4: Id2-deficient CD8+ effector cells rapidly acquire a central memory phenotype.
Figure 5: Diminished clearance of bacteria by Id2-deficient CD8+ effector cells.
Figure 6: Id2-deficient CD8+ effector cells proliferate normally.
Figure 7: Id2-knockout CD8+ effector cells have altered amounts of mRNA of genes that regulate survival.
Figure 8: Stimulation of CD8+ T cells induces increased DNA-binding activity by E proteins.

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Acknowledgements

We thank C. Murre for providing Id2-deficient mice and discussions; S. Hedrick, G. Barton and J. Hamerman for advice and critical review of the manuscript; and D. Mathis, C. Benoist and M. Bevan for their support. Supported by the Cancer Research Foundation (A.W.G.), the V Foundation for Cancer Research (A.W.G.), the US National Institutes of Health (AI067545 to A.W.G.) and the Doris A. Howell Foundation (N.A.L.).

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Author notes

  1. Michael A Cannarile and Nicholas A Lind: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Biological Sciences, University of California, San Diego, La Jolla, 92093, California, USA

    Michael A Cannarile, Nicholas A Lind, Alison D Sheridan, Kristin A Camfield, Bei Bei Wu, Kitty P Cheung, Zhaoqing Ding & Ananda W Goldrath

  2. Department of Molecular Biology, The Scripps Research Institute, La Jolla, 92037, California, USA

    Richard Rivera

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Correspondence to Ananda W Goldrath.

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Supplementary information

Supplementary Fig. 1

Generation of Id2-deficient mice by gene targeting. (PDF 577 kb)

Supplementary Fig. 2

Impaired polyclonal immune response of Id2-deficient CD8+ T cells to Lm-OVA infection. (PDF 1318 kb)

Supplementary Fig. 3

Id2-deficient OT-I thymocytes and splenocytes respond normally to antigen. (PDF 731 kb)

Supplementary Fig. 4

Quantitative PCR comparison of gene expression by Id2-deficient and Id2-wildtype OT-I effector T cells. (PDF 759 kb)

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Cannarile, M., Lind, N., Rivera, R. et al. Transcriptional regulator Id2 mediates CD8+ T cell immunity. Nat Immunol 7, 1317–1325 (2006). https://doi.org/10.1038/ni1403

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