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

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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Correspondence to Ronald N. Germain.

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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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