Submitted January 20, 2005
Returned for revision February 12, 2005
Accepted April 27, 2005
Immunology
Linking Two Immuno-Suppressive Molecules: Indoleamine 2,3
Dioxygenase Can Modify HLA-G Cell-Surface Expression
Alvaro González-Hernandez ,
Joël LeMaoult *,
Ana Lopez ,
Estibaliz Alegre ,
Julien Caumartin ,
Solène Le Rond ,
Marina Daouya ,
Philippe Moreau ,
and
Edgardo D. Carosella
* To whom correspondence should be addressed. E-mail: lemaoult{at}dsvidf.cea.fr.
Abstract
Non-classical HLA-class I molecule HLA-G and indoleamine
2,3 dioxygenase (INDO) have both been shown to play
crucial immunosuppressive roles in fetal-maternal
tolerance, in humans and mice, respectively. HLA-G
inhibits NK and T cell function by high affinity
interaction with inhibitory receptors and INDO acts by
depleting the surrounding micro-environment of the
essential amino acid tryptophan, thus inhibiting T cell
proliferation. We investigated whether HLA-G expression
and INDO function were linked. We found, working with
antigen presenting cell lines and monocytes, that
functional inhibition of INDO by 1-methyl-tryptophan
induced cell-surface expression of HLA-G1 by originally
cell-surface HLA-G1-negative APCs, and that in reverse,
functional boost of INDO by high tryptophan concentrations
induced a complete loss of HLA-G1 cell-surface expression
by originally cell-surface HLA-G1 positive APCs. This
mechanism was shown to be post-translational since 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 implication in fetal-maternal tolerance are
discussed.
Key words:
Embryo •
Immunology •
Trophoblast
