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The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells

Nature Immunology volume 7, pages 475–481 (2006)Cite this article

Abstract

Antigen-specific memory T cells are a critical component of protective immunity because of their increased frequency and enhanced reactivity after restimulation. However, it is unclear whether 'memory-like' T cells generated during lymphopenia-induced homeostatic proliferation can also offer protection against pathogens. Here we show that homeostatic proliferation–induced memory (HP-memory) CD8+ T cells controlled bacterial infection as effectively as 'true' memory CD8+ T cells, but their protective capacity required the presence of CD4+ T cells during homeostatic proliferation. The necessity for CD4 help was overcome, however, if the HP-memory CD8+ T cells lacked expression of TRAIL (tumor necrosis factor–related apoptosis-inducing ligand; also called Apo-2L). Thus, like conventional CD8+ memory T cells, the protective function of HP-memory CD8+ T cells shows dependence on CD4+ T cell help.

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Figure 1: HP-memory T cells provide robust protection against L. monocytogenes infection.
Figure 2: HP-memory T cells from MHC class II–deficient hosts do not protect against bacterial challenge.
Figure 3: Phenotype and functional comparisons show HP-memory OT-I T cells and true memory T cells are similar.
Figure 4: Proliferation and differentiation of HP-memory OT-I T cells after LM-OVA challenge.
Figure 5: TRAIL expression correlates with failure to provide protective immunity.
Figure 6: HP-memory–II-KO cells do not inhibit HP-memory–B6 cells.

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Acknowledgements

We thank T. Griffith for providing TRAIL-deficient mice; and K. Hogquist, M. Jenkins, M. Mescher and members of the Jamequist lab for input. Supported by the National Institutes of Health (S.C.J. and S.P.S.), the Centers for Disease Control (S.C.J.), the American Cancer Society (S.P.S.), the National Cancer Institute (T32 CA009138 to S.E.H.), the American Cancer Society (S.E.H.) and the Irvington Institute (M.C.W.).

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Center for Immunology, Minneapolis, 55454, Minnesota, USA

    Sara E Hamilton & Stephen C Jameson

  2. Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, 92121, California, USA

    Monika C Wolkers & Stephen P Schoenberger

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  1. Sara E Hamilton
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Correspondence to Stephen C Jameson.

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Supplementary information

Supplementary Fig. 1

Experimental scheme. (PDF 314 kb)

Supplementary Fig. 2

Protection against LM-OVA by memory OT-I T cells. (PDF 202 kb)

Supplementary Fig. 3

Functional comparison of HP-memory and true memory OT-I T cells. (PDF 782 kb)

Supplementary Fig. 4

HP-memory T cells derived from Tcra−/− hosts do not provide protection against LM-OVA challenge. (PDF 736 kb)

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Hamilton, S., Wolkers, M., Schoenberger, S. et al. The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells. Nat Immunol 7, 475–481 (2006). https://doi.org/10.1038/ni1326

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