Transcriptome and proteome expression in activated human CD4 and CD8 T-lymphocytes.
T-lymphocytes (T-cells) are unique in that unlike monocytes, they have no insulin receptors, and are insulin insensitive, but upon activation with antigens develop insulin, IGF-1, and IL-2 receptors, and become insulin sensitive tissues. In vivo activation of these cells has now been demonstrated in patients with diabetic ketoacidosis. We analyzed the genomics and proteomics of activated and non-activated CD4+ and CD8+ T-cells of normal subjects using Affymetrix microarray gene chips and proteomes by SELDI-TOF mass spectrometry analysis. Genes for IL-2, insulin, and IGF-1 receptors were increased at least 2-fold in activated vs non-activated T-cells. Using an expression array containing the entire human genome of 39,500 genes, we evaluated approximately 27,000 genes relevant in physiologic and cellular ontologies. Of these, approximately 10,500 genes were increased in activated cells, compared to about 7,000, which were decreased, and approximately 9500, which were unchanged. Among activated ontologies were signal transduction pathways such as IRS-1, IRS-2, Akt, and glycolytic pathways. To our knowledge this is the first report of an hitherto unreported event. Possible implications of these processes are discussed in the light of their physiological significance.
Stentz
Frankie B
FB
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA. fstentz@utmem.edu
Kitabchi
Abbas E
AE
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D020543:Proteome; D012313:RNA / Q000737:chemistry; D018075:RNA, Complementary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism
D007328:Insulin; D007376:Interleukin-2; D020543:Proteome; D018075:RNA, Complementary; D012333:RNA, Messenger; D012313:RNA; D017526:Receptor, IGF Type 1