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

Andrew L. Mellor, Derin B. Keskin, Theodore Johnson, Phillip Chandler, David H. Munn

Research output: Contribution to journalArticle

256 Scopus citations

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 tumorassociated 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.

Original languageEnglish (US)
Pages (from-to)3771-3776
Number of pages6
JournalJournal of Immunology
Volume168
Issue number8
DOIs
StatePublished - Apr 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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