It has been reported that inhibiting glycolysis by metabolic inhibitors such as 2DG (2-Deoxy-D-glucose) and metformin (inhibits complex I of ETC) (Table 1) can considerably decrease [74] the glycolysis of an activated Teff and their cytokine production [101-103]. These two drugs and 6-Diazo-5-oxo-L-norleucine (DON) (Table 1), a glutamine analogue, has been reported to abolish the immune response. In transplant settings, combined therapy such as 2DG, metformin, and DON could suppress the proliferation of pathogenic Teff cells and promote the generation of antigen-specific Tregs; however, combination therapy does not cause the global inhibition of immune responses; instead, it selectively inhibits effector responses while promoting Treg responses based on differential metabolism of immune cells resulted in a specific immune suppression [103]. This combinational therapy targets explicitly allogeneic Teffs that cause graft rejection and keeps other immune cells and healthy tissues relatively unharmed. This combined therapy reduces skin and heart allografts rejection through the inhibition of allogeneic Teffs, and by stimulating Treg proliferation and activation [103-105]. Furthermore, metformin (AMPK agonist) and Soraphen A (acetyl-CoA carboxylase inhibitors) (Table 1) enhance pTreg differentiation by inhibiting allogeneic Teffs in autoimmune mouse models of allergic asthma and experimental allergic encephalomyelitis respectively (Figure 3) [60, 106-109].