Mechanisms of L-selectin regulation by activated T cells
| Autor: | C C Chao, R Jensen, M O Dailey |
|---|---|
| Rok vydání: | 1997 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 159:1686-1694 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.159.4.1686 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|