**6. Other tolerogenic strategies**

Tregs are not the only approach, involved in tolerance establishment in liver transplantation. Other cells also participate in by expressing particular molecules or changing their genetic pattern.

*Regulatory T Cells in the Mosaic of Liver Transplantation Tolerance DOI: http://dx.doi.org/10.5772/intechopen.94362*

In 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals by microarray profiling Martinez-Llordella et al. identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for γδ T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4 + CD25+ T-cells and Vδ1+ T cells) than either non-tolerant patients or healthy individuals [129].

The human leucocyte antigen-G (HLA-G) is a non-classical HLA class I molecule with prominent tolerogenic properties. It inhibits cytotoxicity and proliferation, but stimulates the development of regulatory T cells. HLA-G is present as a membrane-associated form and a soluble one. Interestingly, the uptake of HLA-G by some resting but mostly in activated CD4 and CD8 T cells leads to the instant generation of a new type of regulatory cells that initially act through cell-surface molecules that they temporarily display but do not express themselves [130–132]. This mechanisms is defined as trogocytosis and seems to play important role for the establishment of immune tolerance [133]. Several groups provides evidences about the role of HLA-G in kidney and heart transplantation [134–136]. In healthy conditions in adults, HLA-G is weakly expressed in liver, but it might be transmitted through transendothelial migration and/or trogocytosis from circulating cells under particular circumstances like cytokines, hypoxia etc. [137–139]. In all cases, elevated levels of sHLA-G is associated with reduced risk of rejection and better survival [140, 141].
