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Autocrine IL-2 is required for secondary population expansion of CD8+ memory T cells

Nature Immunology volume 12, pages 908913 (2011) | Download Citation

Abstract

Two competing theories have been put forward to explain the role of CD4+ T cells in priming CD8+ memory T cells: one proposes paracrine secretion of interleukin 2 (IL-2); the other proposes the activation of antigen-presenting cells (APCs) via the costimulatory molecule CD40 and its ligand CD40L. We investigated the requirement for IL-2 by the relevant three cell types in vivo and found that CD8+ T cells, rather than CD4+ T cells or dendritic cells (DCs), produced the IL-2 necessary for CD8+ T cell memory. Il2−/− CD4+ T cells were able to provide help only if their ability to transmit signals via CD40L was intact. Our findings reconcile contradictory elements implicit in each model noted above by showing that CD4+ T cells activate APCs through a CD40L-dependent mechanism to enable autocrine production of IL-2 in CD8+ memory T cells.

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Acknowledgements

We thank S. Salek-Ardakani (La Jolla Institute for Allergy and Immunology) for vaccinia virus–OVA; M.K. Jenkins (University of Minnesota Medical School) for Act-mOVA-transgenic mice; M. Rafii-El-Idrissi for demonstrating how to produce and purify the virus; F. Lambolez for the protocol for purifying T cells from the liver; S. Trifari and M. Pipkin for advice on granzyme B expression; and C. Kim and K. Van Gunst for technical advice and assistance. Supported by the US National Institutes of Health (R01 AI076972 and R01CA81261 to S.P.S.), the Leukemia and Lymphoma Society (1630-06 to S.P.S.) and the Kurz Family Foundation.

Author information

Author notes

    • Ramon Arens

    Present address: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.

Affiliations

  1. Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.

    • Sonia Feau
    • , Ramon Arens
    • , Susan Togher
    •  & Stephen P Schoenberger

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Contributions

S.F., R.A. and S.P.S. designed the experiments; S.F. and R.A. did the experiments with assistance from S.T.; and S.F. and S.P.S. analyzed the data and wrote the manuscript with contributions from R.A.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Sonia Feau.

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DOI

https://doi.org/10.1038/ni.2079