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

• DOI: 10.1046/j.1365-2567.2002.01526.x
• Publication Date: 2003-03-12T02:32:05Z
• Authors: Geon Kook Lee; Hyeon Jin Park; Megan Macleod; Phillip Chandler; David H. Munn; Andrew L. Mellor
• Keywords: ZAP70

Summary 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 chemically defined tryptophan‐free media. Under conditions expressed CD25 CD69 progressed through first 12 hr G0/G1 phase but did not express CD71, cyclin D3, cdk4, begin DNA synthesis, or differentiate into cytotoxic effector cells. In addition, with their growth arrested by tryptophan deprivation exhibited enhanced tendencies die via apoptosis when exposed anti‐Fas antibodies. Apoptosis was inhibited caspase inhibitor observed originated from Fas‐deficient mice. These findings suggest that absence free entered cell cycle progression ceased mid‐G1 became susceptible death apoptosis, part though Fas‐mediated signalling. Thus, mature antigen‐presenting IDO Fas‐ligand may induce antigen‐specific tolerance blocking rapid induction activation induced local tissue microenvironments.