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

controversial. The study of Valencia et al. evidenced that treatment with anti-TNF antibody (infliximab) increases FOXP3 mRNA and protein expression by CD4<sup>+</sup> CD25hi Tregs and restored their suppressive function [106]. Later on, Chen et al. shows that upon in vitro activation with plate-bound anti-CD3 Ab and soluble anti-CD28 Ab, Foxp3 expression by highly purified mouse Tregs is markedly downregulated. TNF partially abrogates this effect and stabilizes Foxp3 expression as this effect of TNF can be blocked by anti-TNFR2 Ab, but not by anti-TNFR1 Ab [107, 108]. In any case, the role of TNF-a needs to be further investigated because TNF-a plays important role in the inflammatory reactions, where Tregs are expected to be also involved.

Upon activation, effector T cells produce IL-2, which stimulates T cells proliferation and the expansion of the immune response. At the same time, Tregs are distinguished by the their high expression of CD25 [109]. These facts suggest that Tregs need IL-2 to survive [110, 111]. Placed in an activated milieu, Tregs may compete with effector cells and as a result, decrease the levels of IL-2 in the environment. In fact, this is the third approach that Tregs apply to achieve a state of suppression [112, 113].

Regulatory T cells apply all of the above-mentioned approaches for the establishment of immune-tolerant milieu. Still, there are no evidences about the mechanism preferred by nTregs or iTregs. Similarly, despite the abundance of data, no specific mechanisms can be attributed to a particular pathologic condition. Probably, the modus operandi of Tregs depends on the finetuning of T-cell receptor-antigen recognition and interaction, the target cell characteristics and the cytokine spectrum in the surrounding milieu.
