Modulation of Tryptophan Catabolism by Human Leukemic Cells Results in the Conversion of Cd25- into Cd25+ T Regulatory Cells.
From: Institute of Hematology and Medical Oncology “L. & A. Serà gnoli,” University of Bologna and Stem Cell Center, S. Orsola-Malpighi Hospital, Bologna, Italy. acurti@alma.unibo.it
Blood
- Publish Date: Apr 2007
- ISSN: 0006-4971
- Volume: 109
- Issue: 7
- Pages: 2871-7
- Medium: Print
- Language: English
- Citation (JAMA): Curti Antonio, Pandolfi Simona, Valzasina Barbara, et al. Modulation of Tryptophan Catabolism by Human Leukemic Cells Results in the Conversion of Cd25- into Cd25+ T Regulatory Cells.. Blood Apr 2007;109:2871-7
Abstract
Indoleamine 2,3-dioxygenase (IDO) is a novel immunosuppressive agent expressed in some subsets of normal and neoplastic cells, including acute myeloid leukemia (AML) cells. Here, we show that IDO expression correlates with increased circulating CD4+CD25+FOXP3+ T cells in patients with AML at diagnosis. In vitro, IDO+ AML cells increase the number of CD4+ CD25+ T cells expressing surface CTLA-4 and FOXP3 mRNA, and this effect is completely abrogated by the IDO inhibitor, 1-methyl tryptophan (1-MT). Purified CD4+CD25+ T cells obtained from coculture with IDO+ AML cells act as T regulatory (T(reg)) cells because they do not proliferate, do not produce interleukin (IL)-2, and inhibit naive T-cell proliferation. Coculture with IDO+AML cells results in the conversion of CD4+CD25- into CD4+CD25+ T cells, which is completely abrogated by 1-MT. Moreover, in mice, intrasplenic injection of IDO+ leukemia/ lymphoma A20 cells induces the expansion of bona fide T(reg) cells by conversion of CD4+CD25- T cells; this effect is counteracted by 1-MT treatment. These data indicate that AML cells induce T-cell tolerance by directly converting CD4+CD25- T cells into CD4+CD25+ T(reg) cells through an IDO-dependent mechanism.
Mesh Headings (Keywords): Adult, Animals, Base Sequence, CD4-Positive T-Lymphocytes, Cell Line, Tumor, Coculture Techniques, DNA Primers, Forkhead Transcription Factors, Gene Expression, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Interleukin-2 Receptor alpha Subunit, Leukemia, Myeloid, Acute, Mice, T-Lymphocytes, Regulatory, Tryptophan
Check for Full Text / PubMed Unique Identifier (PMID): 17164341
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