Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses.

Abstract

Pharmacological inhibition of indoleamine 2,3-dioxygenase (IDO) activity during murine gestation results in fetal allograft rejection and blocks the ability of murine CD8(+) dendritic cells to suppress delayed-type hypersensitivity responses to tumor-associated peptide Ags. These observations suggest that cells expressing IDO inhibit T cell responses in vivo. To directly evaluate the hypothesis that cells expressing IDO inhibit T cell responses, we prepared IDO-transfected cell lines and transgenic mice overexpressing IDO and assessed allogeneic T cell responses in vitro and in vivo. T cells cocultured with IDO-transfected cells did not proliferate but expressed activation markers. The potency of allogeneic T cell responses was reduced significantly when mice were preimmunized with IDO-transfected cells. In addition, adoptive transfer of alloreactive donor T cells yielded reduced numbers of donor T cells when injected into IDO-transgenic recipient mice. These outcomes suggest that genetically enhanced IDO activity inhibited T cell proliferation in vitro and in vivo. Genetic manipulation of IDO activity may be of therapeutic utility in suppressing undesirable T cell responses.

• Authors: Andrew L Mellor, Derin B Keskin, Theodore Johnson, Phillip Chandler, David H Munn
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 168 Issue 8 Pg. 3771-6 (Apr 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 11937528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Differentiation, T-Lymphocyte
• Biomarkers
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Tryptophan Oxygenase

Topics

• Animals
• Antigens, Differentiation, T-Lymphocyte (biosynthesis)
• Biomarkers (analysis)
• Coculture Techniques
• Down-Regulation (genetics, immunology)
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Lymphocyte Activation (genetics)
• Lymphocyte Culture Test, Mixed
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Transgenic
• T-Lymphocytes (immunology)
• Transfection
• Tryptophan Oxygenase (biosynthesis, genetics)
• Tumor Cells, Cultured (enzymology, immunology)
• Up-Regulation (genetics, immunology)