LINOMIDE INHIBITS PROGRAMMED CELL-DEATH OF PERIPHERAL T-CELLS IN-VIVO

Programmed cell death (PCD) is involved in the physiological regulation of lymphocyte turnover, as well in the antigen-driven selection of T and B cells. Here it is shown that the immunomodulator linomide (quinoline-3-carboxamide) inhibits the apoptotic decay of peripheral T lymphocytes in response to three different stimuli. First, linomide reduces the superantigen-mediated apoptosis and deletion of specific T lymphocytes of both the CD4(+) and the CD8(+) subsets without affecting other superantigen-triggered phenomena such as T cell expansion and anergy. Second, linomide abolishes the T lymphopenia and inhibits PCD of splenic CD4(+) and CD8(+) T cells induced by exogenous glucocorticoids. This effect is restricted to peripheral T lymphocytes and does not concern thymocytes. Finally, linomide abolishes the development of lymphopenia that follows infection with vaccinia virus,while reducing PCD of CD4(+) and CD8(+) peripheral T cells. The anti-apoptotic effect of linomide could account for its immunostimulatory properties and might be relevant to the treatment of immunodeficiencies associated with an increased apoptotic decay of T lymphocytes.