First Author | Mellor AL | Year | 2002 |
Journal | J Immunol | Volume | 168 |
Issue | 8 | Pages | 3771-6 |
PubMed ID | 11937528 | Mgi Jnum | J:132898 |
Mgi Id | MGI:3777175 | Doi | 10.4049/jimmunol.168.8.3771 |
Citation | Mellor AL, et al. (2002) Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses. J Immunol 168(8):3771-6 |
abstractText | 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. |