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CD8+ T cell contraction is controlled by early inflammation

Nature Immunology volume 5, pages 809–817 (2004)Cite this article

Abstract

Pathogen-specific CD8+ T cells expand in number after infection and then their numbers invariably contract by 90–95%, leaving a stable memory cell pool. The chief features of this response are programmed early after infection; however, the factors regulating contraction are mostly undefined. Here we show that antibiotic treatment before Listeria monocytogenes infection induced numbers of protective memory CD8+ T cells similar to those in control infected mice, by a pathway without contraction. The absence of contraction correlated with decreased early inflammation and interferon-γ production and an increased fraction of CD8+ T cells expressing the interleukin 7 receptor at the peak of the response. Thus, contraction is controlled by early inflammation but is not essential for the generation of protective memory CD8+ T cells after infection.

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Figure 1: Functional CD8+ T cell memory generation after reduction of bacterial infection by antibiotic treatment at 24 h after infection.
Figure 2: Amp pretreatment does not prevent the generation of CD8+ T cell memory in response to virulent or attenuated L. monocytogenes.
Figure 3: Memory CD8+ T cells generated in Amp-pretreated mice provide protection after secondary L. monocytogenes infection.
Figure 4: CD8+ T cell memory in Amp-pretreated mice without contraction.
Figure 5: Bacterial clearance, in vivo antigen and IFN-γ production after L. monocytogenes infection in control or Amp-pretreated mice.
Figure 6: Lack of contraction in Amp-pretreated mice correlates with increased IL-7R expression on antigen-specific CD8+ T cells and IFN-γ deficiency but not the magnitude of CD8+ T cell expansion.
Figure 7: CpG treatment at the time of L. monocytogenes infection induces contraction of CD8+ T cells in Amp-pretreated mice.
Figure 8: CpG treatment at the time of L. monocytogenes infection does not induce contraction of CD8+ T cells in IFN-γ-deficient mice.

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Acknowledgements

We thank K. Rensberger and R. Podyminogin for technical assistance; R. Ashman and P. Lenert (University of Iowa) for CpG oligonucleotides; and S. Perlman and S. Varga (University of Iowa) for critical review of the manuscript. Supported by National Institutes of Health (AI42767, AI46653 and AI50073 to J.T.H., and T32AI07485 to B.B.P.) and The Leukemia and Lymphoma Society (V.P.B.).

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Authors and Affiliations

  1. Department of Microbiology, University of Iowa, Iowa City, Iowa, USA

    Vladimir P Badovinac & John T Harty

  2. Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA

    Brandon B Porter & John T Harty

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  1. Vladimir P Badovinac
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Correspondence to John T Harty.

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Supplementary information

Supplementary Fig. 1

Ex vivo detection of Ag-specific CD8+ T cells after L. monocytogenes infection. (PDF 30 kb)

Supplementary Fig. 2

LCMV-specific CD8+ T cell response is not altered in Amp-pretreated mice. (PDF 32 kb)

Supplementary Fig. 3

Ag-specific CD8+ T cells in low and high dose infected control mice exhibit similar response kinetics and IL-7R expression. (PDF 34 kb)

Supplementary Fig. 4

Increased Bcl-2 expression on Ag-specific CD8+ T cells in Amp-pretreated mice after L. monocytogenes infection. (PDF 40 kb)

Supplementary Fig. 5

Bacterial clearance and lack of contraction in L. monocytogenes infected IFN-γ-deficient mice after Amp treatment. (PDF 31 kb)

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Badovinac, V., Porter, B. & Harty, J. CD8+ T cell contraction is controlled by early inflammation. Nat Immunol 5, 809–817 (2004). https://doi.org/10.1038/ni1098

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