Estudio de la enzima indolamina -2 3-dioxigenasa en las celulas presentadoras de antigeno modulacion por la sintasa de oxido nitrico y efecto en la expresion de la hla-g y en la tolerancia inmonologica

Resumen

HLA-G and indoleamine 2,3-dioxygenase (IDO) are implicated in immune tolerance. HLA-G inhibits NK and T cell function and IDO inhibits T cell proliferation by tryptophan depletion. Dendritic cells (DC) are strong inducers of immunity but they can al so be tolerogenic. They could express IDO and HLA-G, but without HLA-G surface expression. Nitric oxide (NO) synthases and IDO are expressed monocytes and no could inhibited ido activity causing a possible interference in its biological function. we investigated the links among these molècules, and the effect on immune tolerance.Functional inhibition of ido induced cell-surface expression of HLA-G in monocytes and antigen presenting cell lines. However, either Trp or its metabolites induced HLA-G expression in DC. Besides, immature DC preincubated with Trp and its metabolites have a decreased capacity to stimuíate T celis in mixed lymphocyte reaction. Secondly, NO caused a bimodal effect in ido activity depending on the NO concentrations used: NO at high micromolar concentrations inhibits ido activity and the contrary occurs with low micromolar concentrations, that increase ido activity. The NOS inhibitors and the calmoduline inhibitor W7 also decreased ido activity. The effect of NO in ido activity was not through cGMP production. Besides, immunoprecipitation analysis showed a nitration of the ido protein in monocytic cell lines. These results show that NO regulates ido function in monocytes, and that tryptophan can have two linked modulation vias of the immune system: through ido and through HLA-G, and both molècules can cooperate in the immune suppression.