Franny Jongbloed

154 CHAPTER 6 postoperatively. Our results suggest that bariatric surgery may facilitate partial restoration of this accelerated T-cell aging and thus may help to ameliorate morbidity in morbidly obese patients. The underlying chronic inflammatory state in obesity resembles the consequences of inflammaging as seen in older healthy individuals. Inflammaging affects the immune system, causing a release of cytokines which eventually leads in a vicious circle to increased damage on cells and tissues 28 . Also, the thymus involutes with age resulting in remodeling of the CD4/CD8 T-cell ratio and an enhanced T-cell differentiation state 8,26 . T-cells are part of the adaptive immune system and are derived from lymphoid precursor cells in bone marrow, migrating towards the thymus to further differentiate. In response to infectious agents, either T-helper (CD4 + ) or T-cytotoxic (CD8 + ) cells differentiate from naive to into memory cells to generate a potent second response to the same stimuli. Within the memory T-cell pool, central (CM) and effector memory (EM) T-cells can be distinguished, both with different phenotypical and functional characteristics. CM and EM T-cells are predominant within circulating CD4 + and CD8 + T-cells, respectively 27 . Changes to the T-cell mediated adaptive immunity due to obesity has been shown before, for instance obesity increases both the total numbers of CD4 + and CD8 + T-cells 28 while causing a decrease in CD4 + regulatory T-cells 11,29,30 . The effects of obesity on maturation of the T-cell system has only been investigated in children, where obesity led to an increase in differentiated EM and EMRA T-cells 31 . In patients with renal failure, uremia causes a chronic inflammatory environment inducing a severe depletion of naive T-cells and a shift to more differentiated T-cells, reflected by a decrease in CM and increase in EM and EMRA 15,32,33 . In this study, we show that obesity causes a shift towards fully differentiated T-cell effector memory cells (EMRA) with a much stronger effect in older patients with MetS. Presumably, the number of differentiated T-cells increases with age while the number of naive cells decreases 34 . We confirm the latter, however after correcting for age and the presence of MetS we showed a strikingly different T-cell compartment with a decrease in naive T-cells and a marked increase in EMRA and CD28null T-cells. These results were much more pronounced in the CD8 + T-cell compartment, which is in line with the latest literature showing that the immunological changes due to obesity affect mostly CD8 + T-cells 13 . This pronounced effect of MetS on T-cell immunity and telomere length is of clinical interest, since it enables us to identify patients within the morbidly obese patients who have a potentially increased risk of morbidity and therefore a higher need for surgical intervention.