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Modelling T-cell memory by genetic marking of memory T cells in vivo

Nature volume 399, pages 593–597 (1999)Cite this article

Abstract

Immunological memory is the ability of the immune system to respond with enhanced vigour to pathogens that have been encountered in the past. Following infection or immunization, most effector T cells undergo apoptotic cell death, but a small fraction of these cells, proportional to the early antigen load and initial clonal burst size1, persist in the host as a stable pool of memory T cells2,3,4,5,6,7. The existence of immunological memory has been recognized for over 2,000 years, but our understanding of this phenomenon is limited, primarily because memory lymphocytes cannot be unequivocally identified as they lack specific, permanent markers. Here we have developed a transgenic mouse model system whereby memory T cells and their precursors can be irreversibly marked with a reporter gene and thus can be unambiguously identified. Adoptive transfer of marked CD8+ T cells specific for lymphocytic choriomeningitis virus protected naive recipients following viral challenge, demonstrating that we have marked memory T cells. We also show that cytotoxic effector lymphocytes that develop into memory T cells can be identified in the primary response.

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Figure 1: Transgenic constructs used.
Figure 2: PLAP expression occurs only after Cre-mediated recombination.
Figure 3: Expression of granzyme-B-promoter-driven Cre recombinase in activated T cells.
Figure 4: PLAP expression in CD4+ T cells responding to KLH in vivo.
Figure 5: CD8+ T-cell response to LCMV infection in CD2–STOP–PLAP × granzyme-B–Cre mice.
Figure 6: PLAP+ CD8+ T cells are LCMV-specific.
Figure 7: Adoptive transfer of CD8+ T cell memory.
Figure 8: Memory T cells can be distinguished from recently activated T cells.

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Acknowledgements

We thank C. Roman, I. Stancovski, S. Cherry, K. Alexandroplous, M. Scott, G.Kelsoe, R. Welsh, L. Selin, R. Ahmed and members of the Baltimore laboratory for useful discussions. We also thank T. Ley for p687 plasmid; R. Welsh, R. Ahmed and J. Carlos de la Torre for LCM viral stocks; D. Kioussis for the VahCD2 transgenic construct; M. Brasch for pBS185 and pBS302 plasmids; and A.Nagy for the hCMV-Cre transgenic mice. J.J. Thanks H. Rayburn and W. Sha for teaching him pronuclear injection and transgenesis, and M. Scott for help with adoptive transfers. J.J. was a recipient of a postdoctoral fellowship from the Helen Hay Whitney foundation and is currently a special fellow of the Leukemia Society of America.

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Author notes

  1. Joshy Jacob

    Present address: Emory Vaccine Center and the Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia, 30322, USA

  2. David Baltimore

    Present address: California Institute of Technology, Pasadena, California, 91125, USA

  3. David Baltimore: Correspondence and requests for materials should be addressed to D.B.

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  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Joshy Jacob & David Baltimore

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Correspondence to David Baltimore.

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Jacob, J., Baltimore, D. Modelling T-cell memory by genetic marking of memory T cells in vivo. Nature 399, 593–597 (1999). https://doi.org/10.1038/21208

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