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Initial T cell frequency dictates memory CD8+ T cell lineage commitment

Nature Immunology volume 6, pages 793–799 (2005) Cite this article

Abstract

Memory T cells can be divided into central memory T cell (TCM cell) and effector memory T cell (TEM cell) subsets based on homing characteristics and effector functions. Whether TEM and TCM cells represent interconnected or distinct lineages is unclear, although the present paradigm suggests that TEM and TCM cells follow a linear differentiation pathway from naive T cells to effector T cells to TEM cells to TCM cells. We show here that naive T cell precursor frequency profoundly influenced the pathway along which CD8+ memory T cells developed. At low precursor frequency, those TEM cells generated represented a stable cell lineage that failed to further differentiate into TCM cells. These findings do not adhere to the present dogma regarding memory T cell generation and provide a means for identifying factors controlling memory T cell lineage commitment.

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Figure 1: TEM cells convert to TCM cells when derived from adoptively transferred TCR-transgenic CD8+ T cells.
The alternative text for this image may have been generated using AI.
Figure 2: Endogenous CD8+ T cells generate distinct TCM and TEM lineages in response to infection.
The alternative text for this image may have been generated using AI.
Figure 3: Initial naive CD8+ T cell precursor frequency 'imprints' memory lineage commitment during the primary response.
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Figure 4: Commitment to the TCM and TEM lineages occurs during the primary response.
The alternative text for this image may have been generated using AI.
Figure 5: Proliferative capacity of TEM cells is regulated by clonal competition.
The alternative text for this image may have been generated using AI.

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Acknowledgements

We thank D. Gran and A. Worth for flow cytometry sorting, and Q. Pham for technical assistance. Supported by the National Institutes of Health (AI41576; DK45260 to L.L.; and AI053970 to K.D.K.) and the Edward Jenner Institute for Vaccine Research (publication number 100).

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Authors and Affiliations

  1. Division of Immunology, University of Connecticut Health Center, Farmington, 06030, Connecticut, USA

    Amanda L Marzo, Kimberly D Klonowski & Leo Lefrançois

  2. The Edward Jenner Institute for Vaccine Research, Compton, Newbury, RG20 7NN, Berkshire, UK

    Amanda L Marzo, Agnes Le Bon, Persephone Borrow & David F Tough

Authors
  1. Amanda L Marzo
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  2. Kimberly D Klonowski
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  3. Agnes Le Bon
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  4. Persephone Borrow
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  6. Leo Lefrançois
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Correspondence to Leo Lefrançois.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1 (download PDF )

TEM do not convert to TCM following secondary challenge. (PDF 84 kb)

Supplementary Fig. 2 (download PDF )

Increasing DC numbers results in enhanced TEM generation. (PDF 71 kb)

Supplementary Fig. 3 (download PDF )

Proposed model for the differentiation pathways of TCM and TEM cells. (PDF 119 kb)

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Marzo, A., Klonowski, K., Bon, A. et al. Initial T cell frequency dictates memory CD8+ T cell lineage commitment. Nat Immunol 6, 793–799 (2005). https://doi.org/10.1038/ni1227

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