Mechanisms of L-selectin regulation by activated T cells.
The activation of T cells through the TCR results in the differential regulation of a set of adhesion molecules that dramatically alters lymphocyte migration and tissue localization properties in vivo. L-selectin, the lymph node homing receptor, is central to the control of lymphocyte recirculation. We examined the regulation of L-selectin as a function of time after activation in vitro. Within an hour of stimulation, T cells down regulate L-selectin, with a 90% loss by 4 h, due to accelerated proteolytic cleavage. Over the course of the following 48 h, surface receptor expression increases markedly. This is due to an increase in L-selectin mRNA, which, in turn, results from increased message stability. During the next several days after activation, L-selectin levels decrease, resulting in L-selectin-negative T cells by 5 to 7 days after stimulation. This decrease occurs faster in CD8 than in CD4 T cells. During this phase of regulation, L-selectin message remains stable even as the level of specific mRNA continuously decreases. This indicates that the L-selectin-negative phenotype of T cells late after activation is due to the down-regulation of gene transcription. These results demonstrate that after stimulation through the TCR, the expression of L-selectin changes in a triphasic pattern, with an initial marked decrease, followed by a transient phase of superinduction and then a loss of expression. These changes are regulated through the complex interactions between several mechanisms at the transcriptional, post-transcriptional, and protein turnover levels.
Chao
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CC
Department of Microbiology, University of Iowa College of Medicine, Iowa City 52242, USA.
Jensen
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Dailey
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MO
D000818:Animals; D005260:Female; D019041:L-Selectin / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D012333:RNA, Messenger; D019041:L-Selectin; D011493:Protein Kinase C