Human Primary CD4+T Cells Activated in the Presence of IFN-α2b Express Functional Indoleamine 2,3-Dioxygenase
| Autor: | Fabio Romerio, Sabrina Curreli, Prisco Mirandola, Paola Barion, Davide Zella, Kristi Bemis |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
CD4-Positive T-Lymphocytes
CD3 Complex medicine.medical_treatment T cell Cellular differentiation Immunology Gene Expression CD8-Positive T-Lymphocytes Interferon alpha-2 Biology Lymphocyte Activation Interleukin 21 Virology Gene expression medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase RNA Messenger Indoleamine 2 3-dioxygenase Cells Cultured Kynurenine DNA Primers Messenger RNA Base Sequence Reverse Transcriptase Polymerase Chain Reaction Tryptophan Interferon-alpha Cell Biology Molecular biology Recombinant Proteins Tryptophan Oxygenase Cytokine medicine.anatomical_structure Biochemistry Neoplastic cell |
| Zdroj: | Journal of Interferon & Cytokine Research. 21:431-437 |
| ISSN: | 1557-7465 1079-9907 |
| DOI: | 10.1089/107999001750277916 |
| Popis: | Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the catabolism of tryptophan. By creating a local microenvironment in which levels of tryptophan are low, IDO-expressing antigen-presenting cells (APC) could regulate T cell activation. This may be relevant to control both viral and bacterial replication as well as neoplastic cell growth. Interferon-alpha (IFN-alpha) is an antiviral cytokine affecting cellular differentiation. In addition, it reduces proliferation of CD4(+) T cells by several molecular mechanisms. To dissect the molecular steps responsible for the INF-mediated antiproliferative activity, we sought to determine whether activated primary CD4(+) T cells in the presence of IFN-alpha would produce IDO. We demonstrate 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 (about 2000 copies/150,000 cells), as determined by semiquantitative RT-PCR. When cells were stimulated in the presence of IFN-alpha, expression of IDO mRNA was significantly increased (more than 12,000 copies/150,000 cells). Functional analysis of IDO activity paralleled the results obtained with RT-PCR, demonstrating increased production of active enzyme in CD4(+) T cells stimulated in the presence of IFN-alpha. Our results indicate that IFN-alpha modulates levels of IDO produced by activated CD4(+) T cells. This would likely affect bystander cells by modifying levels of tryptophan in the local microenvironment. |
| Databáze: | OpenAIRE |
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