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

Lee, G. K., Park, H. J., Macleod, M. , Chandler, P., Munn, D. H. and Mellor, A. L. (2002) Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology, 107(4), pp. 452-460. (doi: 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Macleod, Dr Megan
• Authors: Lee, G. K., Park, H. J., Macleod, M., Chandler, P., Munn, D. H., and Mellor, A. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Immunology
• Publisher: Wiley
• ISSN: 0019-2805
• ISSN (Online): 1365-2567
• Published Online: 09 December 2002