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Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites

Nature Medicine volume 10, pages 1104–1110 (2004)Cite this article

Abstract

Infection with Leishmania major induces a protective immune response and long-term resistance to reinfection, which is thought to depend upon persistent parasites. Here we demonstrate that although effector CD4+ T cells are lost in the absence of parasites, central memory CD4+ T cells are maintained. Upon secondary infection, these central memory T cells become tissue-homing effector T cells and mediate protection. Thus, immunity to L. major is mediated by at least two distinct populations of CD4+ T cells: short-lived pathogen-dependent effector cells and long-lived pathogen-independent central memory cells. These data suggest that central memory T cells should be the targets for nonlive vaccines against infectious diseases requiring cell-mediated immunity.

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Figure 1: Central memory CD4+ T cells develop during L. major infection.
Figure 2: CD62L defines functionally distinct populations of CD4+ T cells.
Figure 3: TCM cells mediate protective immunity.
Figure 4: Protective TCM cells are present in ndLNs.
Figure 5: Parasite persistence is required for the maintenance of TEFF cells, but not TCM cells and protective immunity.

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Acknowledgements

We thank K. Joyce for excellent technical assistance, members of the Department of Pathobiology for constructive discussions and D. Artis, C.G. Feng, C.A. Hunter, D. Jankovic, E.J. Pearce, S.L. Reiner, H. Shen and A. Sher for critical reading of the manuscript. This work was supported by US National Institutes of Health grant AI35914 (to P. S.).

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Author notes

  1. Colby Zaph and Jude Uzonna: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathobiology, University of Pennsylvania, 3800 Spruce Street, Philadelphia, 19104, Pennsylvania, USA

    Colby Zaph, Jude Uzonna & Phillip Scott

  2. Department of Molecular Microbiology, Washington University, 660 South Euclid Avenue, St. Louis, 63110, Missouri, USA

    Stephen M Beverley

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  1. Colby Zaph
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  2. Jude Uzonna
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Correspondence to Phillip Scott.

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Supplementary information

Supplementary Fig. 1

Homing to LNs is not required for effector T cell function during chronic infection with L. major (PDF 59 kb)

Supplementary Fig. 2

CD4+ T cells mediate infection-induced immunity (PDF 44 kb)

Supplementary Fig. 3

Characterization of CD4+ T cells from naive and immune B6 mice prior to adoptive transfer (PDF 44 kb)

Supplementary Fig. 4

Leishmania-specific IFN-γ and IL-2 responses by CD62Lhigh and CD62Llow CD4+ T cells (PDF 42 kb)

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Zaph, C., Uzonna, J., Beverley, S. et al. Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites. Nat Med 10, 1104–1110 (2004). https://doi.org/10.1038/nm1108

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