Current dogma implies that the ability of memory T cells to respond rapidly to repeat encounters with antigen is due to a minimal requirement for co-stimulation and antigen. However, a new study suggests that naive CD8+ T cells, but not central memory CD8+ T cells, proliferate in response to low levels of antigen. This study shows that although both naive and memory T cells are stimulated by low antigen doses in vivo, only naive T cells enter the cell cycle. This effect is intrinsic to naive T cells owing to the degradation of the cyclin-dependent kinase inhibitor p27 and the activation of cell cycle effectors in response to low antigen levels. Compared with naive T cells, central memory T cells less efficiently activate the T cell receptor (TCR) signalling component ZAP70, have lower levels of surface TCR and have higher levels of protein tyrosine phosphatases that inhibit TCR signalling. Together, this suggests that memory CD8+ T cells require stronger TCR stimulation than naive CD8+ T cells to enter the cell cycle, which may safeguard against harmful reactions to self antigen.
References
Mehlhop-Williams, E. R. & Bevan, M. J. Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation. J. Exp. Med. http://dx.doi.org/10.1084/jem.20131271 (2014)
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Bird, L. Memory cells need more (not less) antigen. Nat Rev Immunol 14, 139 (2014). https://doi.org/10.1038/nri3639
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DOI: https://doi.org/10.1038/nri3639