T and B Cell Composition and Cytokine Producing Capacity Before and After Bariatric Surgery

Abstract

Morbid obesity is associated with a chronic state of low-grade inflammation, which may lead to accelerated differentiation of T and B cells. These differentiated immune cells are strongly cytotoxic and have an increased pro-inflammatory cytokine producing capacity. Furthermore, the anti-inflammatory function of the T and B cells decreases. The aim of this study was to evaluate the effect of morbid obesity on the subset profile and cytokine producing capacity of T and B cells. Subsequently, we assessed whether bariatric surgery affected the subset profile and cytokine producing capacity of these cells. We determined the proportion of T and B cell subsets and their cytokine producing capacity in peripheral blood collected from 23 morbidly obese patients before and three months after bariatric surgery using flow-cytometry. We compared this with the results of 25 lean controls. Both CD4+ and CD8+ T cells showed a more differentiated subset profile in morbidly obese patients as compared to lean controls, which was not recovered three months after bariatric surgery. The B cell composition of morbidly obese patients after bariatric surgery adjusted towards the profile of lean controls. However, the IL-2 and IFN-γ producing capacity of CD8+ T cells and the IL-2, IFN-γ, TNF-α and IL-10 producing capacity of B cells was not restored three months after bariatric surgery. In conclusion, the data suggest that the immune system has the capacity to recover from the detrimental effects of morbid obesity within three months after bariatric surgery in terms of cell composition; however, this was not seen in terms of cytokine producing capacity. The full restoration of the immune system after bariatric surgery may thus take longer.

Distinct B cell profiles characterise healthy weight and obesity pre- and post-bariatric surgery

“…This strategy enabled us to identify the following populations within the CD19 + B cell compartment: IgD + CD27 − naïve, IgD − CD27 + class-switched and IgD + CD27 + unswitched memory, IgD − CD27 − DN cells, CD24 hi CD38 hi transitional, CD24 int CD38 int mature, CD24 hi CD38 lo total memory, CD24 lo CD38 lo activated B cells, and CD24 int CD38 hi pre-plasmablasts. As reported previously (12,22), we found a signi cant expansion of IgD + CD27 − naïve B cells in individuals with obesity compared to lean controls, which was normalised to control levels following surgery (Fig. 1a).…”

“…Bariatric surgery, indicated as an intervention for obesity (6), is associated with signi cant and sustained weight loss, as well as improved metabolic health and reduction in circulating in ammatory factors long-term (7)(8)(9)(10)(11). More recent studies have started to address the impact of bariatric surgery on immune compartments (12)(13)(14)(15).…”

“…Only a limited number of studies have investigated select aspects of B cell activation in obese individuals and there is even greater scarcity of investigations into the impact of bariatric surgery and weight loss on the B cell compartment. Obesity-associated alterations include an increase in mature naïve B cells (12,22) as well as a reduction in total and IL-10 producing transitional B cells (23). Notably, IL-10 production is a key phenotypic feature of B cells with immunoregulatory function (24).…”

Lipotoxicity as a Barrier for T Cell-Based Therapies

“…All these imbalances can have an impact on tumor and immune cells. For instance, T cell proliferation and counts are decreased, and the T cell subset composition is altered in obese as compared to lean individuals in non-cancer-related settings [ 22 , 23 , 24 , 25 , 26 ]. For instance, Wijingaarden et al reported a shift from naïve T cells and effector memory cells re-expressing CD45RA T cells (T EMRA ) towards a higher proportion of central-memory T cells (T CM ) for CD4 + Tells in morbidly obese patients compared to lean controls.…”

“…Contrarily, these patients also showed a higher proportion of CD8 + naïve T cells, effector memory T cells (T EM ) and T EMRA as well as a decreased T CM compartment. Of note, cytokine production of IL-2 and IFN-γ was decreased in CD8 + but not CD4 + T cells in those patients compared to lean controls [ 26 ]. Obesity affects T cell formation already in the thymus, resulting in accelerated thymic aging and a limited T cell repertoire [ 27 ].…”