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Indoleamine 2,3 dioxygenase and human leucocyte antigen‐G inhibit the T‐cell alloproliferative response through two independent pathways
Author(s) -
Le Rond Solène,
Gonzalez Alvaro,
Gonzalez Ana S. L.,
Carosella Edgardo D.,
RouasFreiss Nathalie
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02224.x
Subject(s) - indoleamine 2,3 dioxygenase , kynurenine , human leukocyte antigen , immune system , antigen , t cell , biology , immune tolerance , immunology , microbiology and biotechnology , chemistry , tryptophan , biochemistry , amino acid
Summary Both human leucocyte antigen (HLA)‐G and indoleamine 2,3 dioxygenase (IDO) are key molecules involved in immune tolerance. HLA‐G is a non‐classical HLA class I molecule that can be expressed in both membrane‐bound (HLA‐G1) and soluble (HLA‐G5) forms, both of which exhibit tolerogenic properties via interaction with inhibitory receptors present on natural killer (NK) cells, T cells and antigen‐presenting cells (APC). IDO is an enzyme that acts by depleting the surrounding microenvironment of the essential amino acid, tryptophan, thereby inhibiting T‐cell proliferation. Our present study was aimed at analysing the potential link that may exist between IDO and HLA‐G. Our results showed that during allogeneic reactions, soluble HLA‐G expression was not regulated by the addition of IDO substrate (i.e. tryptophan), metabolite (i.e. kynurenine) or inhibitor (i.e. 1‐methyl‐tryptophan), that IDO activity was not altered by HLA‐G5 treatment, and that HLA‐G5‐mediated inhibition of the T‐cell alloproliferative response was neither affected by the presence of tryptophan and kynurenine nor reversed after IDO activity blockage, demonstrating that HLA‐G5 can exert its function in the absence of functional IDO. Similarly, inhibition of the T‐cell alloresponse, induced by HLA‐G1‐expressing antigen‐presenting cells, was not altered by IDO metabolites or inhibitor. Taken together, these findings show that the function and expression of IDO and HLA‐G5 are not mutually influenced, but rather inhibit the T‐cell alloproliferative response through two independent pathways. IDO and HLA‐G are thus complementary for inducing and maintaining immune tolerance in physiological (pregnancy) and pathological (tumour and allograft) situations.