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Linking Two Immuno-Suppressive Molecules: Indoleamine 2,3 Dioxygenase Can Modify HLA-G Cell-Surface Expression¹

Clínica Universitaria de Navarra,⁴ 31080 Pamplona, Navarra, Spain Service de Recherches en Hémato-Immunologie,⁵ CEA-DSV-DRM, Institut Universitaire d'Hématologie, Hôpital Saint Louis, 75010 Paris, France

Nonclassical human leukocyte antigen (HLA) class I molecule HLA-G and indoleamine 2,3 dioxygenase (INDO) in humans and mice, respectively, have been shown to play crucial immunosuppressive roles in fetal-maternal tolerance. HLA-G inhibits natural killer and T cell function by high-affinity interaction with inhibitory receptors, and INDO acts by depleting the surrounding microenvironment of the essential amino acid tryptophan, thus inhibiting T cell proliferation. We investigated whether HLA-G expression and INDO function were linked. Working with antigen-presenting cell (APC) lines and monocytes, we found that functional inhibition of INDO by 1-methyl-tryptophan induced cell surface expression of HLA-G1 by HLA-G1-negative APCs that were originally cell-surface negative, and that in reverse, the functional boost of INDO by high concentrations of tryptophan induced a complete loss of HLA-G1 cell surface expression by APCs that were originally cell-surface HLA-G1-positive. This mechanism was shown to be posttranslational because HLA-G protein cell contents remained unaffected by the treatments used. Furthermore, HLA-G cell surface expression regulation by INDO seems to relate to INDO function, but not to tryptophan catabolism itself. Potential implications in fetal-maternal tolerance are discussed.

embryo, immunology, trophoblast

² Correspondence. FAX: 33 014 803 1960; lemaoult{at}dsvidf.cea.fr

³ These authors contributed equally to this work