Regulation of T cell immunity by cells expressing indoleamine 2,3-dioxygenase

Abstract

Previous studies suggest that !DO-mediated tryptophan depletion is a mechanism that inhibits T cell responses in vitro and in vivo. To further investigate the effects of cells expressing the tryptophan catabolizing enzyme IDO on T cell responses in vitro we have generated IDO transfected murine cell lines and tested their ability to activate T cells in co-cultures. Cell lines stably transfected with vector sequences alone maintain the ability of parental cell lines to stimulate proliferation of viable T cells. In contrast, cell lines transfected with IDO were unable to stimulate T cell division but induced cell cycle entry determined by CD69 expression. To investigate IDO regulation of T cell immunity in vivo we have generated murine IDO transgenic (L33 -Tg) mice. IDO transgenic mice inhibited in vivo proliferation of adoptively transferred anti-H2-Kb reactive T cell receptor Tg BM3 T cells and anti H-Y reactive Al, T cells. This data demonstrates that IDO induced tryptophan degradation is a mechanism that regulates T cell responses and may provide the basis of a new therapeutic approach in the treatment of autoimmune diseases and cancer. IDO mechanism may also aid transplant patients and inhibit deleterious immune responses.