[On the mechanisms of human T cell proliferation induced by the 10B4 molecule].
The 10B4 system of human T cells seems to constitute a member of T cell receptor complex. We have analyzed the mechanisms by which a monoclonal antibody against the 10B4 molecule activates human peripheral T cells. The 10B4 antibody together with goat anti-mouse immunoglobulin antibody induced significant increase of DNA and RNA syntheses in T cells with peak responses on day 9 and on day 7, respectively. This activation process is mediated by interleukin 2 (IL-2) and its receptor (IL-2R), because (1) IL-2 activity was detected in the culture supernatants, (2) the percentage of IL-2R positive cells increased during the culture period, with a peak on day 9, and (3) the 10B4-induced T cell proliferation was inhibited by anti IL-2R antibody. Blocking studies with pharmacological agents showed that in the 10B4-induced system, a protein kinase C (PK-C) inhibitor, palmitoylcarnitine, blocked DNA synthesis, RNA synthesis, IL-2 production and IL-2R expression whereas a Ca ion channel blocker, verapamil, inhibited DNA synthesis, RNA synthesis, IL-2 production but not IL-2R expression. It is thus concluded that PK-C activation is required for IL-2 production and IL-2R expression and that channel-mediated Ca ion influx is important for IL-2 production but may not be needed for IL-2R expression.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D010172:Palmitoylcarnitine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology*; D014700:Verapamil / Q000494:pharmacology
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D010172:Palmitoylcarnitine; D004247:DNA; D014700:Verapamil; D011493:Protein Kinase C; D002118:Calcium