Human primary CD4(+) T cells activated in the presence of IFN-alpha 2b express functional indoleamine 2,3-dioxygenase

Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the catabo lism of tryptophan, By creating a local microenvironment in which levels of tryptophan are low, IDO-expressing antigen-presenting cells (APC) could re gulate T cell activation. This may be relevant to control both viral and ba cterial replication as well as neoplastic cell growth. Interferon-alpha (TF N-alpha) is an antiviral cytokine affecting cellular differentiation. In ad dition, it reduces proliferation of CD4(+) T cells by several molecular mec hanisms. To dissect the molecular steps responsible for the INF-mediated an tiproliferative activity, we sought to determine whether activated primary CD4(+) T cells in the presence of IFN-alpha would produce IDO, We demonstra te here that IDO mRNA is not present in resting CD4(+) T cells. Stimulation with anti-CD3 plus interleukin-2 (IL-2) induces expression of IDO mRNA (ab out 2000 copies/150,000 cells), as determined by semiquantitative RT-PCR, W hen cells were stimulated in the presence of IFN-alpha, expression of IDO m RNA was significantly increased (more than 12,000 copies/150,000 cells). Fu nctional analysis of IDO activity paralleled the results obtained with RT-P CR, demonstrating increased production of active enzyme in CD4(+) T cells s timulated in the presence of IFN-alpha, Our results indicate that IFN-alpha modulates levels of IDO produced by activated CD4(+) T cells. This would l ikely affect bystander cells by modifying levels of tryptophan in the local microenvironment.