Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses.
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.
Mellor
Andrew L
AL
Program in Molecular Immunology, Institute of Molecular Medicine and Genetics, Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA. amellor@mail.mcg.edu
Keskin
Derin B
DB
Johnson
Theodore
T
Chandler
Phillip
P
Munn
David H
DH
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015415:Biomarkers / Q000032:analysis; D018920:Coculture Techniques; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008213:Lymphocyte Activation / Q000235:genetics; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014366:Tryptophan Oxygenase / Q000096:biosynthesis* / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000201:enzymology* / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014366:Tryptophan Oxygenase