DIFFERENTIAL EFFECT ON POLYAMINE METABOLISM IN MITOGEN-ACTIVATED AND SUPERANTIGEN-ACTIVATED HUMAN T-CELLS

Polyamines are important for regulation of lymphocyte differentiation and proliferation. Mitogens induce synthesis of ornithine decarboxylas e (ODC), the rate limiting enzyme in polyamine biosynthesis. Since mit ogens stimulate T-cells by non-physiological routes, the role of polya mine metabolism in T-cell receptor (TCR)-mediated T-cell activation ha s not been adequately evaluated. The effect of phytohemagglutinin (PHA ) and staphylococcal enterotoxin B (SEB) on T-cell ODC and polyamine s ynthesis was compared. ODC activity was 6-11-fold higher in PHA compar ed to SEB stimulated T-cells. These differences were not attributed to differences in the magnitude of T-cell proliferation. Kinetics of ODC and polyamine synthesis were also different in PHA- and SEB-stimulate d T-cells. In PHA-stimulated cells ODC levels and the induction of put rescine and spermidine synthesis peaked 6 h prior to peak IL-2 product ion, while in SEB-stimulated cells, ODC levels and polyamine synthesis peaked 6-12 h after IL-2 production. Differences in the temporal rela tionship between IL-2 production and polyamine induction in mitogen- v ersus superantigen-stimulated cells may account for the significant in hibition of the proliferative response by alpha-difluoromethylornithin e following PHA but not SEB stimulation. Polyamine metabolism is regul ated differently in T-cells stimulated via TCR engagement than with po lyclonal mitogens. (C) 1998 Elsevier Science B.V. All rights reserved.