Titre
Molecular mechanisms involved in T cell activation. II. The phosphatidylinositol signal-transducing mechanism mediates antigen-induced lymphokine production but not interleukin 2-induced proliferation in cloned cytotoxic T lymphocytes
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kozumbo, W. J.
Auteure/Auteur
Harris, D. T.
Auteure/Auteur
Gromkowski, S.
Auteure/Auteur
Cerottini, J. C.
Auteure/Auteur
Cerutti, P. A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
1987-01
Volume
138
Numéro
2
Première page
606
Dernière page/numéro d’article
12
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 15
Research Support, Non-U.S. Gov't --- Old month value: Jan 15
Résumé
The phospholipid metabolism of cloned murine cytotoxic T lymphocytes (CTL) was examined under conditions in which the induction of proliferation by interleukin 2 (IL 2) and the stimulated production of lymphokine (macrophage-activating factor (MAF] by concanavalin A (Con A) and specific antigen occurred independently of each other. Activation of the CTL by either of the latter two stimuli resulted in changes in the metabolism of phosphatidylinositol (PI) that were early (less than 2.5 min), specific, and prolonged (6 to 8 hr). These changes were primarily characterized by an increase in phosphatidic acid (PA) and PI, with a decrease in phosphatidylinositol-4,5-bisphosphate. The duration of these phospholipid responses, particularly PA and PI, approximated the minimum time of CTL-stimulus interaction required to produce maximal titers of MAF. No changes were observed in other major classes of phospholipids during 8 hr of continuous stimulation. Stimulation with an irrelevant antigen had no effect on CTL phospholipid metabolism. In contrast to specific antigen or Con A, the T cell growth factor IL 2 failed to elicit specific and early biosynthetic responses from PA and PI. Instead, there were nonspecific biosynthetic responses from all major phospholipid classes (including phosphatidylcholine and phosphatidylethanolamine, as well as PA and PI) which occurred between 1 and 6 hr after IL 2 stimulation. Both 1,2-diacylglycerol (DAG) and inositol phosphates (IP), the hydrolytic products of PI turnover, were produced in response to MAF-inducing stimuli, but neither were detected in response to the proliferative stimulus IL 2. Together, these results indicate that the hydrolysis of PI and the concomitant production of the putative second messengers DAG and IP are involved in signaling the production of lymphokines (MAF) by CTL. On the other hand, the failure of IL 2 to elicit a full-spectrum PI response suggests that signals mediating CTL proliferation may utilize an alternate and still undefined pathway.
Sujets
PID Serval
serval:BIB_309A87A7DDDB
PMID
Date de création
2008-01-28T10:13:27.075Z
Date de création dans IRIS
2025-05-20T16:31:23Z