In transplantation, donor-specific tolerance is a crucial parameter for a high survival rate, which could be achieved by increasing Tregs or by suppressing donor reactive T cells. Therefore, the differences in the metabolism between effector and regulatory T cells make immuonometabolism a promising therapeutic intervention that could allow for a more specific immune tolerance in the field of transplantation [47]. Numerous preclinical models of autoimmune diseases and transplantation have shown that Treg cells maintain peripheral tolerance after tissue injury and exposure to intracellular antigens or alloantigen [48]. Various T cells adjust their metabolic programming to meet the energetic demands necessary for their cellular functions. As discussed in the earlier section, for respiration, a naïve T cell mainly depends on OXPHOS, and later on, upon antigen encounter, T cell activates aerobic glycolysis necessary for effector cytokine production [47, 49]. Activated T cells use aerobic glycolysis as a fast generating energetic mechanism to satisfy the immediate energetic demands for proper proliferation and differentiation. This use of aerobic glycolysis by T cells was first described by Otto Warburg in cancer cells and hence is known as the Warburg effect [50]. The two main subsets of T cells (CD4+ and CD8+ T cells) show many similarities in their activation. Both activated subsets enhance their dependency on glycolysis and increase Glut1 expression for glucose uptake; however, they have different metabolic profiles. CD8+ T cells rely on glycolysis less than CD4+ T cells due to diminished glycolytic enzyme expression [51, 52]. Alternatively, CD4+ T cells display a marked increase in mitochondrial mass as compared to CD8+ T cells, while CD8+ T cells show greater dependency on OXPHOS for cytokine production [53]. Activated CD4+ T cells differentiate into Teffs (Th1, Th2, or Th17 cells) by triggering different metabolic pathways downstream of the TCR and by the availability of essential metabolites.