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The Journal of Immunology, 2002, 168: 3771-3776.
Copyright © 2002 by The American Association of Immunologists

Cells Expressing Indoleamine 2,3-Dioxygenase Inhibit T Cell Responses1

Andrew L. Mellor2,*,{dagger}, Derin B. Keskin*,{dagger}, Theodore Johnson*,{dagger}, Phillip Chandler*,{dagger} and David H. Munn*,{dagger},{ddagger}

* Program in Molecular Immunology, Institute of Molecular Medicine and Genetics, and Departments of {dagger} Medicine and {ddagger} Pediatrics, Medical College of Georgia, Augusta, GA 30912

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.




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