Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division

Immunology. 2002 Dec;107(4):452-60. doi: 10.1046/j.1365-2567.2002.01526.x.


Cells expressing indoleamine 2,3-dioxygenase (IDO), an enzyme which catabolizes tryptophan, prevent T-cell proliferation in vitro, suppress maternal antifetal immunity during pregnancy and inhibit T-cell-mediated responses to tumour-associated antigens. To examine the mechanistic basis of these phenomena we activated naïve murine T cells in chemically defined tryptophan-free media. Under these conditions T cells expressed CD25 and CD69 and progressed through the first 12 hr of G0/G1 phase but did not express CD71, cyclin D3, cdk4, begin DNA synthesis, or differentiate into cytotoxic effector cells. In addition, activated T cells with their growth arrested by tryptophan deprivation exhibited enhanced tendencies to die via apoptosis when exposed to anti-Fas antibodies. Apoptosis was inhibited by caspase inhibitor and was not observed when T cells originated from Fas-deficient mice. These findings suggest that T cells activated in the absence of free tryptophan entered the cell cycle but cell cycle progression ceased in mid-G1 phase and T cells became susceptible to death via apoptosis, in part though Fas-mediated signalling. Thus, mature antigen-presenting cells expressing IDO and Fas-ligand may induce antigen-specific T-cell tolerance by blocking T-cell cycle progression and by rapid induction of T-cell activation induced cell death in local tissue microenvironments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Apoptosis / immunology*
  • Blotting, Western / methods
  • Cell Division / immunology
  • Cell Line / immunology
  • Cytotoxicity, Immunologic / immunology
  • Flow Cytometry / methods
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interphase / immunology
  • Mice
  • Mice, Inbred CBA
  • Mice, Transgenic
  • S Phase / immunology
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Tryptophan / deficiency*
  • Tryptophan Oxygenase / immunology


  • Antigens, CD
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Tryptophan
  • Tryptophan Oxygenase