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

Details

Serval ID
serval:BIB_309A87A7DDDB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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
Journal
Journal of Immunology
Author(s)
Kozumbo  W. J., Harris  D. T., Gromkowski  S., Cerottini  J. C., Cerutti  P. A.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
01/1987
Volume
138
Number
2
Pages
606-12
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 15
Abstract
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.
Keywords
Animals Antigens/immunology Clone Cells Concanavalin A/pharmacology Diglycerides/metabolism Inositol Phosphates/physiology Interleukin-2/pharmacology *Lymphocyte Activation/drug effects Lymphokines/*biosynthesis Macrophage Activation Macrophage-Activating Factors Mice Phosphatidic Acids/metabolism Phosphatidylinositols/*physiology Receptors, Antigen, T-Cell/physiology T-Lymphocytes, Cytotoxic/immunology/*physiology Time Factors
Pubmed
Web of science
Create date
28/01/2008 11:13
Last modification date
20/08/2019 13:15
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