De novo emergence of growth factor receptors in activated human CD4+ and CD8+ T lymphocytes.
Using phytohemagglutinin (PHA)-activated human T lymphocytes, we have demonstrated de novo emergence of growth factor receptors (insulin, insulin-like growth factor-1 [IGF-1], and interleukin-2 [IL-2]) in the CD4(+) and CD8(+) subsets determined by flow cytometry. This activation was also associated with development of insulin-degrading activity (IDA) in a time-dependent fashion. These events, which are actinomycin- and cycloheximide-sensitive, occur only in activated, but not nonactivated, CD4(+) and CD8(+) lymphocytes. The emergence of these receptors, as well as IDA, which is preceded by CD69 emergence, reaches a plateau by 72 hours and is comparable in both subsets. The IDA is localized in the cytosol, and insulin binding is limited to the cell membrane. T-lymphocyte activation also initiates expression of the IL-2 gene with the transcription of IL-2 mRNA, the level of which is further enhanced by 38% with the addition of insulin. In these activated lymphocytes, insulin binding to its receptor also caused an 83% upregulation of phosphorylated insulin receptor substrate-1 (IRS-1). In situ development of these growth factor receptors and signal transduction mechanisms in T lymphocytes upon activation, such as by proinflammatory cytokines or oxidative stress, could be an important defense mechanism in various disease states in man.
Stentz
Frankie B
FB
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Tennessee Health Science Center, Memphis 38163, USA.
Kitabchi
Abbas E
AE
D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis; D011972:Receptor, Insulin / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D015375:Receptors, Interleukin-2; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin