Differential role of CTLA-4 in regulation of resting memory versus naive CD4 T cell activation - PubMed (original) (raw)
Comparative Study
. 1998 Dec 1;161(11):5855-61.
Affiliations
- PMID: 9834064
Comparative Study
Differential role of CTLA-4 in regulation of resting memory versus naive CD4 T cell activation
D P Metz et al. J Immunol. 1998.
Abstract
Regulation of peripheral T cell responses is critical for preserving self tolerance. Memory T cells have a lower threshold for activation through the TCR and are thought to be less dependent on costimulation than naive T cells, suggesting a requirement for more stringent regulation of memory T cells. We have recently shown that CD4 engagement apart from the TCR results in the inactivation of memory, but not naive, CD4 T cells. We show here that this inhibition requires ligation of CTLA-4, in that blocking CTLA-4-B7 interactions restores memory CD4 T cell responsiveness. Early signaling through CTLA-4 is possible because resting memory, but not naive, CD4 T cells contain intracellular stores of CTLA-4 that are continuously recycled between the cytoplasm and the cell surface. This mechanism ensures that low intensity TCR engagements, which are thought to be important for peripheral T cell longevity, do not cause memory T cell activation but instead raise their threshold for costimulatory signals. This may give memory T cells an extended lifespan with a reduced risk of inappropriate activation.
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