Activated CD4+T cells enter the splenic T-cell zone and induce autoantibody-producing germinal centers through bystander activation

CD4+T (helper) cells migrate in huge numbers through lymphoid organs. However, little is known about traffic routes and kinetics of CD4+T-cell subsets within different organ compartments. Such information is important because there are indications that CD4+T cells may influence the function of microenvironments depending on their developmental stage. Therefore, we investigated the migration of resting (naïve), activated, and recently activated (memory) CD4+T cells through the different compartments of the spleen. Resting and recently activated CD4+T cells were separated from thoracic duct lymph and activated CD4+T cells were generated in vitro by cross-linking the T-cell receptor and CD28. The present study shows that all three CD4+T-cell subsets selectively accumulate in the T-cell zone of the spleen. However, only activated T cells induce the formation of germinal centers (GCs) and autoantibodies in rats and mice. Our results suggest that in a two-step process they first activate B cells independent of the T-cell receptor repertoire and CD40 ligand (CD154) expression. The activated B cells then form GCs whereby CD154-dependend T-cell help is needed. Thus, activated T cells may contribute to the development of autoimmune diseases by activating autoreactive B cells in an Ag-independent manner. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim

Activated CD4+T cells enter the splenic T-cell zone and induce autoantibody-producing germinal centers through bystander activation

CD4+T (helper) cells migrate in huge numbers through lymphoid organs. However, little is known about traffic routes and kinetics of CD4+T-cell subsets within different organ compartments. Such information is important because there are indications that CD4+T cells may influence the function of microenvironments depending on their developmental stage. Therefore, we investigated the migration of resting (naïve), activated, and recently activated (memory) CD4+T cells through the different compartments of the spleen. Resting and recently activated CD4+T cells were separated from thoracic duct lymph and activated CD4+T cells were generated in vitro by cross-linking the T-cell receptor and CD28. The present study shows that all three CD4+T-cell subsets selectively accumulate in the T-cell zone of the spleen. However, only activated T cells induce the formation of germinal centers (GCs) and autoantibodies in rats and mice. Our results suggest that in a two-step process they first activate B cells independent of the T-cell receptor repertoire and CD40 ligand (CD154) expression. The activated B cells then form GCs whereby CD154-dependend T-cell help is needed. Thus, activated T cells may contribute to the development of autoimmune diseases by activating autoreactive B cells in an Ag-independent manner. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim

The Impact of Body Weight Changes versus Exercise Capacity Changes on Health-Related Factors following a Lifestyle Intervention in Employees with Metabolic Syndrome

Background: Lifestyle changes are a cornerstone in the treatment of metabolic syndrome (MetS). However, evidence as to which components of the MetS and associated aspects of quality of life are driven by weight loss or improvements in exercise capacity are scarce. Methods: Company employees (n = 302, 48.2 ± 8.2 years, BMI 33.2 ± 5.4 kg/m2) with diagnosed MetS were evaluated after a 6-month telemonitoring-supported intervention (counselling in nutrition and physical activity) or wait-list control (delayed start of the same intervention). Results: Exercise capacity, body mass index (BMI), and MetS severity were improved after the intervention. Multivariable regression models revealed that changes in BMI were associated with changes in three components of MetS (waist circumference, triglycerides, blood glucose), whereas changes in exercise capacity only were associated to one MetS component change (systolic blood pressure) but also improvements in anxiety severity, aspects of quality of life, and work ability. Conclusions: Both physical activity promotion and diet should be part of a holistic treatment of patients with MetS. However, our data suggest that dietary-induced weight loss might be more successful when aiming at improving MetS risk factors, whereas focusing more on physical activity promotion might be preferred when targeting aspects in quality of life and mental health