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CD4+ T cell survival is not directly linked to self-MHC–induced TCR signaling

Nature Immunology volume 1, pages 329–335 (2000)Cite this article

Abstract

T cell receptor (TCR) signaling triggered by recognition of self-major histocompatibility complex (MHC) ligands has been proposed to maintain the viability of naïve T cells and to provoke their proliferation in T cell–deficient hosts. Consistent with this, the partially phosphorylated state of TCRζ chains in naïve CD4+ and CD8+ T cells in vivo was found to be actively maintained by TCR interactions with specific peptide-containing MHC molecules. TCR ligand-dependent phosphorylation of TCRζ was lost within one day of cell transfer into MHC-deficient hosts, yet the survival of transferred CD4+ lymphocytes was the same in recipients with or without MHC class II expression for one month. Thus, despite clear evidence for TCR signaling in nonactivated naïve T cells, these data argue against the concept that such signaling plays a predominant role in determining lymphocyte lifespan.

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Figure 1: Analysis of naïve TCRζ (ζ here and in all figures) chain phosphorylation.
Figure 2: Maintenance of phosphorylated TCRζ in CD4+ T cells requires MHC class II and specific peptides.
Figure 3: Maintenance of phosphorylated TCRζ in naïve CD4+ T cells requires CD4–MHC class II interactions.
Figure 4: Maintenance of phosphorylated TCRζ in naïve CD8+ T cells depends on MHC class I.
Figure 5: Survival of CD4+ T cells one month after transfer.

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Acknowledgements

We thank R. Swofford, C. Eigsti and D. Stephany of the NIAID Flow Cytometry Facility for cell sorting; A. Fox for technical assistance; D. Raulet, P. Schwartzberg, P. Love, J. Delon, A. Porgador and C. Broussard for discussions and reading the manuscript; B. Rocha, R. Schwartz, B. J. Fowlkes and members of the Germain lab for helpful discussion; C. Doyle, J. Riberdy, L. Van Kaer and E. Bikoff for mice; J. Bolen, A. Iwasaki and B. Kelsall for reagents; and G. Asfaw, F. Bishop and C. Callahan for assistance with typing mice.

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Author notes

  1. Koji Yasutomo

    Present address: Department of Pediatrics, School of Medicine, University of Tokushima, Kuramoto 3, Tokushima, 770, Japan

  2. Jeffrey R. Dorfman and Irena Štefanová: These authors contributed equally to this work.

Authors and Affiliations

  1. Lymphocyte Biology Section, Laboratory of Immunology, Building 10 Room 11N311

    Ronald N. Germain

  2. National Institutes of Health, Bethesda, 20892, MD, USA

    Ronald N. Germain

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  1. Jeffrey R. Dorfman
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Dorfman, J., Štefanová, I., Yasutomo, K. et al. CD4+ T cell survival is not directly linked to self-MHC–induced TCR signaling. Nat Immunol 1, 329–335 (2000). https://doi.org/10.1038/79783

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