Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division
Open Access
- 9 December 2002
- journal article
- research article
- Published by Wiley in Immunology
- Vol. 107 (4), 452-460
- https://doi.org/10.1046/j.1365-2567.2002.01526.x
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- Functional expression of indoleamine 2,3-dioxygenase by murine CD8α+ dendritic cellsInternational Immunology, 2002
- Functional Characterization of Jurkat T Cells Rescued from CD95/Fas-Induced Apoptosis through the Inhibition of CaspasesBiochemical and Biophysical Research Communications, 2000
- Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation?Immunology Today, 1999
- IL-12 Acts Directly on DC to Promote Nuclear Localization of NF-κB and Primes DC for IL-12 ProductionImmunity, 1998
- A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis.The Journal of Experimental Medicine, 1996
- Effects of different antigenic microenvironments on the course of CD8+ T cell responses in vivoInternational Immunology, 1996
- Inhibition of collagenase and stromelysin gene expression by interferon-gamma in human dermal fibroblasts is mediated in part via induction of tryptophan degradation.JCI Insight, 1995
- Activation-induced apoptosis in human macrophages: developmental regulation of a novel cell death pathway by macrophage colony-stimulating factor and interferon gamma.The Journal of Experimental Medicine, 1995
- Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or β-globin gene promotersInternational Immunology, 1994
- The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells.The Journal of Experimental Medicine, 1992