Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6); other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease.

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The role of natural killer (NK) cells in solid organ transplantation is not well established, although several recent reports highlight the importance of the activating receptor NKG2D and its ligands in the development of rejection during transplantation. The human NKG2D ligands (MICA and MICB) are induced in allografts during acute and chronic rejection, and the presence of anti-MICA antibodies is correlated with a higher incidence of rejection. The binding of these ligands to its receptor NKG2D activates NK cells, enhances the functions of effectors, and allows NK cells to function as a bridge between innate and adaptive immunity associated with the transplantation. In fact, blockage of NKG2D with the anti-NKG2D monoclonal antibodies prolongs graft survival and prevents CD28-independent rejection in heart and skin allograft mouse models. Furthermore, the current immunosuppressive therapies can modulate the expression of NK cell receptors and consequently the effector functions of NK cells. That is particularly important during the first few months after transplantation, when the susceptibility to opportunistic viral infections is higher and NKG2D has an essential role. In this review, we analyze in detail the potential role of the NKG2D-activating receptor and its ligands in the immune responses during the outcome of solid organ transplantation. These findings open a new pathway for therapeutic intervention that can contribute to tolerance in solid organ transplantation.

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The activating receptor NKG2D is mainly expressed on γδ T, αβ CD8+ T, NKT and NK cells but an unusual NKG2D+ CD4+ T subset has been detected in certain pathologies. In this work, we analyzed the presence of CD4+ NKG2D+ T cells in peripheral blood samples from kidney transplanted patients and healthy donors by flow cytometry. Furthermore, whole genome microarray expression studies (Human HT-12 v3, Illumina) and TCR Vβ repertory (TCR Landscape technology) were performed in order to determinate its phenotypic and functional characteristics. We showed that 41% of the patients have a subset of CD4+ NKG2D+ T lymphocytes, which maintains stable during time. These cells presented a phenotype of memory cells with downregulation of costimulatory molecules and an increased expression of cytotoxic markers specific of NK cells. Several pathways associated with immune response, apoptosis, inflammatory response and cellular catabolic process were significant affected. CD4+ NKG2D+ T cells showed resistance to apoptosis and restricted TCR repertoire with oligoclonal expansion of one or two Vβ families, suggesting a limited capacity to respond to different antigens. In short, presence of this subset in kidney transplanted patients could be favorable for the graft acceptance but compromise the immune response against diverse antigens. It could be used as a biomarker to determine the outcome of the allograft and predict the immune response in these patients.