We have been studying how IL 1 controls gene transcription, and conclude that many of IL 1's effects on a variety of cell types are mediated by the transcription factor AP-1. IL 1 activates AP-1 in several ways: 1) first, performed AP-1 proteins are activated, 2) these induce the promoter for the AP-1 component, c-jun and 3) the mRNA for c-jun is stabilized. These actions result in production of high levels of AP-1 factors, which subsequently trigger the promoters of other genes, such as IL 2. Lymphocytes have the unique ability to rearrange genes that are used for immune recognition. Little is understood of the rearrangement mechanism because it has not been possible to observe this process in vitro. We have developed an in vitro organ culture in which extensive rearrangement of the VBeta genes occurs in 24-48 hr. T lymphocytes are critical to survival, yet little is known of how the body controls their production. We have taken various approaches to try to accelerate T cell production. IL 1 had the ability to stimulate pre-T cells to proliferate in vitro and develop the CD4 marker, but was not effective in vivo. We now find that growth hormone promotes expansion of post-thymic T cells in vivo, and this will be used in a clinical trial in AIDS patients.
