Ligand-activated T cell growth factor-induced proliferation: absorption of T cell growth factor by activated T cells.
The fate in culture of the T cell growth factor (TCGF), which is required for continued growth of human cultured T cells (CTC) in vitro, was studied. TCGF activity was stable for 7 days at 37 degrees C. However, it was no longer detectable after incubation with actively growing CTC at 37 degrees C for 3 days. This loss of TCGF activity also occurred quite rapidly and was detectable within 1 hr of incubation of 0.3 ml supernatant with 2 to 5 x 10(7) CTC at 23 degrees C. 2 x 10(8) mononuclear peripheral blood leukocytes were not effective in removing TCGF activity, and incubation with similar numbers of cells from B and T cell lines had no effect. Three-day-old concanavalin A and phytohemagglutinin blasts were very reactive with TCGF, so that 10(7) or 2 x 10(7) cells consistently removed TCGF activity. These experiments suggested specific absorption of TCGF by activated T cells, and led us to develop a model of ligand-activated TCGF-induced proliferation of T cells: Ligands induce production of TCGF by T-producer cells and deliver a first signal to the T-responder cells. This causes a receptor for TCGF to appear on T-responder cells. Only then does TCGF deliver the obligatory second signal that is needed to drive the T-responder cells into proliferation.
D000042:Absorption; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D003470:Culture Media; D004306:Dose-Response Relationship, Immunologic; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008024:Ligands / Q000494:pharmacology*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D003470:Culture Media; D006133:Growth Substances; D008024:Ligands; D010835:Phytohemagglutinins; D010664:Phenylmethylsulfonyl Fluoride