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Programmed contraction of CD8+ T cells after infection

Nature Immunology volume 3, pages 619–626 (2002)Cite this article

Abstract

The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of antigen-specific CD8+ T cell expansion and the ensuing contraction to a stable number of memory cells. We show that CD8+ T cell expansion after Listeria monocytogenes infection was primarily dependent on the initial infection dose or amount of antigen displayed, and was also influenced by the rate of pathogen clearance. However, the onset and kinetics of CD8+ T cell contraction after L. monocytogenes and lymphocytic choriomeningitis virus infections were independent of the magnitude of expansion, dose and duration of infection or amount of antigen displayed. Thus, major features of antigen-specific CD8+ T cell homeostasis, including the contraction phase of an immune response, may be programmed early after infection.

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Figure 1: Relationship between CD8+ T cell expansion and contraction.
Figure 2: Measurement of antigen load.
Figure 3: Effect of decreasing pathogen persistence on CD8+ T cell contraction.
Figure 4: Effect of prolonged infection on CD8+ T cell contraction.
Figure 5: Effect of persistent infection on CD8+ T cell contraction.
Figure 6: Functional memory cells from LCMV-infected Pfp−/− mice
Figure 7: Contraction of primary and secondary CD8+ T cell responses after infection.
Figure 8: Contraction of primary and secondary CD8+ T cell responses in the same host.

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Acknowledgements

We thank E. Gutierrez for technical assistance, the NIH Tetramer Core Facility for MHC class I tetramers and S. Perlman for critical review of the manuscript. Supported by the Leukemia and Lymphoma Society (V. P. B.) and NIH grants AI42767, AI46653, AI50073 (to J. T. H) and T32A07485 (to B. B. P.).

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Authors and Affiliations

  1. Department of Microbiology, University of Iowa, Iowa City, 52242, IA, USA

    Vladimir P. Badovinac & John T. Harty

  2. Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, 52242, IA, USA

    Brandon B. Porter & John T. Harty

Authors
  1. Vladimir P. Badovinac
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  3. John T. Harty
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Correspondence to John T. Harty.

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Supplementary information

Web Fig. 1.

Onset of antigen-specific CD8+ T cell contraction after infection with different strains of L. monocytogenes. (a) BALB/c mice were infected with indicated doses of 10403s (virulent), DP-L1936 (plcAB-deficient), XFL303ActA (actA-deficient) and DP-L1942 (actA-deficient) and the total number of LLO + p60-specific CD8+ T cells in the spleen was determined by intracellular cytokine staining for IFN-γ. Mice that contained viable bacteria in the liver at day 7 after infection are marked (*). Data represent mean ± s.d. of three mice per group per time point. (b) Contraction of antigen-specific CD8+ T cells in the spleen at the indicated time points after L. monocytogenes infection was normalized to the peak of the primary response (day 7); presented as 100%. (JPG 42 kb)

Web Fig. 2.

Visualizing primary and secondary CD8+ T cell responses in the same host. (a) BALB/c Thy1.2 mice were infected with LCMV-Armstrong. One-hundred days later splenocytes (1 × 107) from LCMV memory mice were transferred into naïve BALB/c Thy1.1 mice. Two days after transfer recipient BALB/c Thy1.1 mice were infected with 1 or 0.1 LD50 of XFL303. (b) Frequency of Thy1.2 NP(118–126)-specific CD8+ T cells before and after transfer into naïve Thy1.1 mice. (c) Total number of CD8+ Thy1.2+ and NP(118–126)-specific CD8+ Thy1.2+ cells before and after the transfer. Numbers represent the percentage of transferred CD8+ and NP(118–126)-specific cells in the spleens of mice that received 107 donor cells. (JPG 36 kb)

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Badovinac, V., Porter, B. & Harty, J. Programmed contraction of CD8+ T cells after infection. Nat Immunol 3, 619–626 (2002). https://doi.org/10.1038/ni804

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