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Oral intake of protein leads to tolerance through the induction of regulatory T cells (Tr cells) in mesenteric lymph nodes (MLNs). Here we show that the inhibition of cyclooxygenase-2 (COX-2) in vivo suppressed oral tolerance and was associated with enhanced differentiation of interleukin (IL)-4-producing T cells and reduced Foxp3+ Tr-cell differentiation in MLN. As a result, the functional suppressive capacity of these differentiated mucosal T cells was lost. IL-4 was causally related to loss of tolerance as treatment of mice with anti-IL-4 antibodies during COX-2 inhibition restored tolerance. Dendritic cells (DCs) in the MLN differentially expressed COX-2 and reductionist experiments revealed that selective inhibition of the enzyme in these cells inhibited Foxp3+ Tr-cell differentiation in vitro. Importantly, the inhibition of COX-2 in MLN-DC caused increased GATA-3 expression and enhanced IL-4 release by T cells, which was directly related to impaired Tr-cell differentiation. These data provide crucial insights into the mechanisms driving de novo Tr-cell induction and tolerance in the intestine.Mucosal Immunology (2009) 2, 254–264; doi:10.1038/mi.2009.2; published online 4 March 2009 [ABSTRACT FROM AUTHOR]

Although as pretreatment oral tolerance is a potent means to achieve systemic suppression, its application in ongoing disease is controversial. Here we propose that availability of naive T cells may critically determine whether immunological tolerance is achieved during ongoing antigenic reactivity. Infusion of naive antigen-specific T cells into mice directly prior to eliciting a secondary Th2 response induces these naive cells to actively engage in the antigenic response despite presence of established memory. Naive antigen-specific T-cells divided faster, produced more interleukin (IL)-2, IL-4 and IL-5 and enhanced immunoglobulin E (IgE) release during a secondary Th2 response, compared with naive T cells that were infused prior to a primary response. Despite such contribution by new cohorts of naive T cells co-infusion of mucosal Tr together with naive T cells could suppress enhanced IgE release during a secondary Th2 response. We conclude that naive T cells contribute to a secondary Th2 response and although they can still be suppressed in the presence of sufficient numbers of mucosal Tr, they may interfere with potential therapeutic application of mucosal tolerance. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate obesity classifications from body fat percentage (BF%), body mass index (BMI), and waist circumference (WC).Methods: A total of 451 overweight/obese active duty military personnel completed all three assessments.Results: Most were obese (men, 81%; women, 98%) using National Institutes of Health (NIH) BF% standards (men, >25%; women, >30%). Using the higher World Health Organization (WHO) BF >35% standard, 86% of women were obese. BMI (55.5% and 51.4%) and WC (21.4% and 31.9%) obesity rates were substantially lower for men and women, respectively (p < 0.05). BMI/WC were accurate discriminators for BF% obesity (theta for all comparisons >0.75, p < 0.001). Optimal cutoff points were lower than NIH/WHO standards; WC = 100 cm and BMI = 29 maximized sensitivity and specificity for men, and WC = 79 cm and BMI = 25.5 (NIH) or WC = 83 cm and BMI = 26 (WHO) maximized sensitivity and specificity for women.Conclusions: Both WC and BMI measures had high rates of false negatives compared to BF%. However, at a population level, WC/BMI are useful obesity measures, demonstrating fair-to-high discriminatory power. [ABSTRACT FROM AUTHOR]