In the present study, we investigated the role of tumor necrosis factor receptor II (TNF-RII) in human T cell activation induced via the T cell receptor (TCR) in an antigen-presenting cell-independent system. Our results confirm that interaction of TNF-alpha with TNF-RII but not TNF-RI is directly costimulatory to TCR-mediated T cell activation, thereby augmenting T cell proliferation, expression of T cell activation markers (CD25, human leukocyte antigen-DR, TNF-RII), and secretion of cytokines such as interferon-gamma and TNF-alpha. In contrast to the well-defined costimulatory molecule CD28, costimulation via TNF-RII showed significant differences in kinetics, requirement for cross-linking, redundancy of intracellular signaling pathways involved, and the capacity to induce interleukin (IL)-2, IL-10, and IL-13 secretion. In addition, cross-linking TNF-RII had the capacity to down-regulate TCR/CD28-induced Ca++ mobilization, IL-2 mRNA expression, and IL-2 and IL-10 secretion. Taken together, our findings demonstrate that TNF-RII plays a unique role among the T cell costimulatory molecules, as TNF-RII ligation can have positive and negative effects on TCR-dependent signaling. TNF-RII cross-linking has an inhibitory effect on early TCR signaling events proximal to induction of Ca++ flux, which ultimately leads to modulation of the T cell cytokine pattern expressed.

SUMMARYAbsolute and relative NK cell numbers were determined in peripheral whole blood by flow cytometry in patients with common variable immunodeficiency (CVID) (n 55) and X-linked agammaglobulinaemia (XLA) (n 19) on regular immunoglobulin (IVIG) therapy. Absolute CD3 2 CD16 1 NK cell numbers were significantly reduced in CVID patients (median 108/ml, range 23±815), compared with normal subjects (n 60) (289/m l, range 56±640, P , 0´001). Total lymphocyte concentrations were significantly lower in CVID (median 1587/ml, range 523±7519) compared with normal subjects (median 2019/ml, range 1124±3149, P 0´004), with the percentage of NK cells also being significantly decreased (median 7´5%, range 3´0±33´0%, compared with 14´2%, range 2´6±30´8%, P , 0´001). In XLA, absolute NK cell numbers (median 140/ml, range 32±551, P , 0´001) but not relative numbers were significantly reduced compared with normal controls. We excluded the possibility that IVIG interferes with in vitro binding of CD16 MoAbs. Further analysis of NK cell subsets showed a deficiency of both CD16 1 and CD56 1 cells in CVID, most marked in the CD3 2 CD8 dim subpopulation, which may be due to increased homing of these cells to the gut. Serial studies on a small number of patients suggest that IVIG therapy has no short-term effect on NK cells, although we cannot exclude an effect with prolonged use. Although there are no obvious clinical effects of the NK depletion in CVID and XLA, this may be a factor in their predisposition to cancer.Keywords natural killer cells CD16 common variable immunodeficiency X-linked agammaglobulinaemia intravenous immunoglobulin therapy interferon-gamma

BackgroundThe Internet is widely available and commonly used for health information; therefore, Web-based weight loss programs could provide support to large parts of the population in self-guided weight loss. Previous studies showed that Web-based weight loss interventions can be effective, depending on the quality of the program. The most effective program tools are visual progress charts or tools for the self-monitoring of weight, diet, and exercises. KiloCoach, a commercial program currently available in German-speaking countries, incorporates these features. A previous investigation showed that the program effectively supports users in losing weight.ObjectiveWe investigated weight loss dynamics stratified by weight loss success after 6-month use of KiloCoach. Furthermore, we analyzed possible associations between intensity of program use and weight loss. The results are intended for tailoring user recommendations for weight-loss Internet platforms.MethodsDatasets of KiloCoach users (January 1, 2008 to December 31, 2011) who actively used the platform for 6 months or more were assigned to this retrospective analysis. Users (N=479) were 42.2% men, mean age of 44.0 years (SD 11.7), with a mean body mass index (BMI) of 31.7 kg/m2 (SD 3.2). Based on the weight loss achieved after 6 months, 3 success groups were generated. The unsuccessful group lost <5%, the moderate success group lost 5%-9.9%, and the high success group lost ≥10% of their baseline body weight. At baseline, the unsuccessful (n=261, 54.5%), moderate success (n=133, 27.8%), and high success (n=85, 17.8%) groups were similar in age, weight, BMI, and gender distribution.ResultsAfter 6 months, the unsuccessful group lost 1.2% (SD 2.4), the moderate success group lost 7.4% (SD 1.5), and the high success group lost 14.2% (SD 3.8) of their initial weight (P<.001). Multivariate regression showed that early weight loss (weeks 3-4), the total number of dietary protocols, and the total number of weight entries were independent predictors for 6-month weight reduction (all P<.001) explaining 52% of the variance in weight reduction. Sensitivity analysis by baseline carried forward method confirmed all independent predictors of 6-month weight loss and reduced the model fit by only 11%. The high success group lost weight faster and maintained weight loss more efficiently than the other groups (P<.001). Early weight loss was associated with weight maintenance after 1 year and 2 years (both P<.001). Weight dynamics did not differ between men and women over 6 months when adjusted for baseline and usage parameters (P=.91). The percentage of male long-term users was unusually high (42.2%).ConclusionsOur results suggest that early weight loss and close program adherence (ie, 5 dietary protocols per week and weekly entering of current weight), especially in the early phase of program usage, can improve weight loss outcome.

Objective: To examine the weight-loss success associated with distinct dietary patterns and to determine changes of these dietary patterns during participation in a web-based weight-reduction programme. Design: Factor analysis was used to identify the dietary patterns of twenty-two food groups that were administered in 14 d dietary protocols at baseline and after 3 months. Successful weight loss (≥5 % of initial weight) and BMI were calculated. Logistic regression analyses were used to assess the rates of weight-loss success from each dietary pattern and changing or remaining in the initial dietary pattern. A generalised linear mixed model was used to estimate the effects of changing or staying in a dietary pattern on change in BMI. Subjects: Adults (n 1635) aged 18-81 years. Setting: Users of a web-based weight-reduction programme (2006)(2007)(2008)(2009)(2010)(2011)(2012). Results: Participants who aligned to a healthful dietary pattern at baseline (OR = 1·8; 95 % CI 1·5, 2·3) and after 3 months (OR = 1·5; 95 % CI 1·2, 1·9) had a greater chance of successfully losing weight. After adjusting for age, sex, initial dietary pattern and BMI, participants who started with or changed to the healthful dietary pattern had a greater chance of being successful (OR = 1·4; 95 % CI 1·1, 1·7) and a higher BMI reduction of 0·30 (95 % CI 0·2, 0·5) kg/m 2 compared with those who started with or changed to the energy-dense or high-carbohydrate dietary pattern. Conclusions: A favourable healthful dietary pattern at the beginning and after 3 months was positively associated with anthropometry. However, successful weight loss was feasible in each dietary pattern. Key words Dietary patternsWeight loss Factor analysis Online weight-reduction programme In Europe, more than 50 % of men and women are overweight (1) . A BMI above 30 kg/m 2 is present in 21 % of women and 22 % of men aged 20 years or older (2) . Moreover, worldwide, the prevalence of obesity has almost doubled between 1980 and 2008 (1) . Obesity is an important health risk for diseases such as diabetes mellitus type 2, hypertension, CVD and others (3) . Nevertheless, weight is adjustable, and a moderate weight reduction of 5-10 % is associated with enhanced health benefits (4) . Weight gain is the result of an imbalance between energy intake and expenditure; however, the effect of different dietary factors on weight gain or weight loss remains unclear (5)

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