Autoimmune, insulin-dependent diabetes mellitus in man is an inherited disease . Many studies have demonstrated (reviewed in references 1, 2) that genes linked to the MHC of man contribute to the genetic susceptibility to diabetes . >90% of Caucasian patients suffering from type 1 diabetes express the DR3 and/or DR4 antigens as compared with a 60% expression in the total population . Interestingly, DR3/DR4 heterozygotes are particularly susceptible to the development of diabetes since up to 50% of type 1 diabetics possess this genotype as compared with only 5% of the general population . The fine specificity of the association of DR3 and DR4 with diabetes has recently been defined using HLA restriction endonuclease fragment length polymorphisms (3-5) and human T lymphocyte clones that define DR subtypes (6, 7).The autoimmune response in type 1 diabetes is characterized by insulitis, which is an inflammatory infiltrate affecting the islets of Langerhans . In a study of 60 recent-onset type 1 diabetics, insulitis was present in 78% of patients (8).A persistence of memory cells specific for insulin-producing a cells is suggested by the observation that long-term insulin-dependent patients receiving a pancreas transplant from an identical twin will still reject the islet tissue even though the original antigenic stimulus has been absent for years (9).Recently, two animal models exhibiting spontaneous diabetes mellitus have been identified . The BB rat (10, 11) and the nonobese diabetic (NOD)' mouse (12-16) both evidence the destructive autoimmune pancreatic insulitis that is characteristic of human type 1 diabetes . In the BB rat model, diabetes can be adoptively transferred with Con A-activated splenic lymphocytes obtained from diabetic BB rats (17,18). Further evidence supporting the autoimmune etiology of diabetes in the BB rat is that treatment of BB rats with a combination of immunosuppressive agents, which included cyclosporine A, glucocorticoids, and
Interferons (IFN) have been shown to modulate the expression of a number of cell surface antigens on macrophages and lymphocytes. Because such phenotypic alterations may be involved in the functional effects of IFN, it appears important to characterize further these alterations. In the present work, we evaluated the response to IFN of Ly-6-encoded molecules on murine T cells. Two types of Ly-6 antigens, Ly-6A and Ly-6C, normally present on minor subsets of mature T cells were studied. It was found that in vivo treatment of mice with the IFN inducer poly(I . C) or with purified IFN-alpha/beta resulted two days later in augmented expression of these antigens. Purified T cells cultured in vitro for 2 days in the presence of 5% serum from poly(I . C)-treated mice or of 10(4) units/ml IFN-alpha/beta also displayed dramatically increased (4-12-fold) amounts of Ly-6 antigens. Under the same conditions, the T cell markers Thy-1, Ly-1, Lyt-2 and MT4 were unaffected or slightly diminished while surface expression of H-2 or beta 2-microglobulin antigens was increased by only 10-36%. Therefore, poly(I . C)-induced or purified IFN interacts with resting T cells to selectively enhance Ly-6 antigen expression. This phenomenon was found to correlate functionally with increased proliferative response of the T cells, in presence of phorbol myristate acetate, to anti-Ly-6 antibodies cross-linked on their surface. Enhancement of Ly-6 antigen expression on T cells may thus play a role in IFN-mediated immunoregulation.
Parks can play an important role in youth activity. This study used observational data to evaluate the relationship of environmental and social determinants to youth physical activity intensity levels in Las Vegas neighborhood parks. System for observing play and leisure activity in youth was used to code activity levels as sedentary, walking, or vigorous in five low-income and five high-income parks. Environmental determinants included amenities, incivilities, size, high-speed streets, sidewalk condition, and temperature. Social determinants included percent minority and Hispanic, gender, and income. A multinomial logistic regression model was performed. We observed 1,421 youth, 59% male, 41% female; 21% were sedentary, 38% walking, and 41% vigorous. Males were more likely to be observed walking (OR 1.42) and vigorous (OR 2.21) when compared to sedentary. High-speed streets (OR 0.76), sidewalks condition (OR 0.34), and low-income neighborhoods (OR 0.07) was associated with decreased odds of vigorous activity; incivilities (OR 1.34) and amenities (OR 1.27) were associated with greater odds of being vigorous. Environmental and social determinants are associated with physical activity intensity levels at parks. Stakeholders should ensure quality parks, as they relate to physical activity levels in youth. Understanding environmental and social determinants that influence physical activity at parks is critical to utilizing their full potential in an effort to combat childhood obesity.
Trail use increased about 33% during the 1-year study period for the intervention. Adding wayfinding and incremental distance signage appeared to support the increase in usage which followed the marketing campaign.
Surface molecules encoded by the murine Ly-6 locus can transduce triggering signals in T cells and thus may play important roles in T cell function. Previously, we found that Ly-6 molecules are up-regulated by interferon (IFN)-alpha/beta in resting T cells. Here, we examined the possible influence of IFN-gamma on these molecules. Purified T cells from C57BL/6 (Ly-6.2) and BALB/c (Ly-6.1) mice were incubated in vitro with recombinant murine IFN-gamma and the expression of Ly-6 antigens was measured by flow cytofluorometry. It was found that both Ly-6A/E and T cell-activating protein (TAP) molecules are markedly enhanced while Ly-6C is less affected. Under the same conditions, other T cell surface molecules showed no or marginal changes. The effect of IFN-gamma on Ly-6A/E and TAP expression reached a maximum with as little as 10 U/ml and required only 18-24 h of incubation. Moreover, the enhancement of Ly-6A expression induced by IFN-gamma was stable for at least 5 days. Analysis of T cell subsets further revealed that IFN-gamma-induced augmentation of Ly-6A (C57BL/6 mice) involves both Lyt-2+ and L3T4+ cells while the increase of Ly-6E (BALB/c mice) is more pronounced in Lyt-2+ cells. The functional consequence of these phenotypic alterations was evaluated by studying the mitogenic responses of T cells to antibody-mediated Ly-6 cross-linking in the presence of phorbol myristate acetate. Pretreatment of resting T cells with IFN-gamma dramatically increased the responses to anti-Ly-6A and anti-Ly-6E monoclonal antibodies. IFN-gamma treatment also boosted the stimulation induced by anti-TAP monoclonal antibody when this stimulation was performed under suboptimal conditions. Therefore, IFN-gamma selectively up-regulates the Ly-6A/E and TAP activation pathways in resting T cells. We speculate that this effect may contribute to the immunoregulatory activities of IFN-gamma.
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