To: tnsaf who wrote (76 ) 8/30/1998 2:58:00 PM From: scaram(o)uche Respond to of 1475
Jason: Thank you, thank you, thank you! Wow. It wasn't there a couple of days ago. It used to take about three months to get a Medline reference into the database, back in the days of Grateful Med. I have recently noticed stuff showing up at PubMed virtually days after publication. We increasingly have access to very powerful tools. The work..... good stuff, a very new concept to me. However, we'd still be talking a generalized immunosuppressant. The BTRN concept involves only the elimination of cells that are reacting with antigen at the time of anti-CD2 administration (I am not saying that I've seen sufficient evidence that it will work). Here's something related...... Infect Immun 1994 Sep;62(9):3705-3711 Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence. Beatty WL, Belanger TA, Desai AA, Morrison RP, Byrne GI Department of Medical Microbiology and Immunology, University of Wisconsin, Madison 53706. Previous studies have shown that the immune-regulated cytokine gamma interferon (IFN-gamma) activates host cells to restrict intracellular growth of the bacterial pathogen Chlamydia trachomatis by induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Recently, subinhibitory levels of IFN-gamma were used to generate an in vitro persistent chlamydial infection characterized by large aberrant, noninfectious reticulate bodies from which infectious progeny could be recovered following the removal of IFN-gamma. Studies were done to determine if the mechanism functioning to induce chlamydiae to enter a persistent state in the presence of low levels of IFN-gamma was similar to that reported to inhibit chlamydial growth. Host cells treated with levels of IFN-gamma required to induce persistence were assessed for IDO activity by high-performance liquid chromatography analysis of tryptophan and its catabolic products. Substantial tryptophan catabolism was detected in acid-soluble cellular pools, indicating that the intracellular availability of this essential amino acid was limited under these conditions. In addition, a mutant cell line responsive to IFN-gamma but deficient in IDO activity was shown to support C. trachomatis growth, but aberrant organisms were not induced in response to IFN-gamma treatment. Analyses of infected cells cultured in medium with incremental levels of exogenous tryptophan indicated that persistent growth was induced by reducing the amount of this essential amino acid. These studies confirmed that nutrient deprivation by IDO-mediated tryptophan catabolism was the mechanism by which IFN-gamma mediates persistent growth of C. trachomatis.