55,694 research outputs found
The Relationship between Well-Being and Technology among Senior Citizens in Indiana
Across America technology has become an ever present requirement for day-to-day living. Senior citizens for this study were those who were 50 years of age and older and were often hindered in understanding and using technology. The purpose of this research study was to determine if there is a statistical significant correlation between the number of technology classes a senior citizen takes and general well-being. Senior citizens were surveyed to determine if understanding of technology changed level of well-being. A paper survey was used with a convenience sample of seniors who take technology based courses through an organization designed to teach the aging population how to use technology. Well-being was measured using two different instruments. The first was the Quality of Life and Enjoyment and Satisfaction Questionnaire- Short Form. The second was the Warwick-Edinburgh Mental Well-being Scale. A Spearmanâs rho correlation was used to determine if there is a relationship between well-being and the number of technology courses taken by seniors. The researcher found that there was a statistically significant moderate-to-strong positive correlation between the number of technology courses completed and overall score on the Quality of Life and Enjoyment and Satisfaction Questionnaire- Short Form. The researcher found there was a statistically significant moderate-to-strong positive correlation number of technology course completed and overall score on the Warwick-Edinburgh Mental Well-being Scale
Plasmodium yoelii infection of BALB/c mice results in expansion rather than induction of CD4+ Foxp3+ regulatory T cells
Recently, we demonstrated elevated numbers of CD4(+) Foxp3(+) regulatory T (Treg) cells in Plasmodium yoeliiâinfected mice contributing to the regulation of antiâmalarial immune response. However, it remains unclear whether this increase in Treg cells is due to thymusâderived Treg cell expansion or induction of Treg cells in the periphery. Here, we show that the frequency of Foxp3(+) Treg cells expressing neuropilinâ1 (Nrpâ1) decreased at early timeâpoints during P. yoelii infection, whereas percentages of Helios(+) Foxp3(+) Treg cells remained unchanged. Both Foxp3(+) Nrpâ1(+) and Foxp3(+) Nrpâ1(â) Treg cells from P. yoeliiâinfected mice exhibited a similar Tâcell receptor VÎČ chain usage and methylation pattern in the Tregâspecific demethylation region within the foxp3 locus. Strikingly, we did not observe induction of Foxp3 expression in Foxp3(â) T cells adoptively transferred to P. yoeliiâinfected mice. Hence, our results suggest that P. yoelii infection triggered expansion of naturally occurring Treg cells rather than de novo induction of Foxp3(+) Treg cells
Regulatory T cell proliferative potential as novel marker to investigate immune tolerance and clinical progression in Multiple Sclerosis
In autoimmune disorders such as Multiple Sclerosis (MS) one of the determining alteration is the breakdown of self-antigen immune-tolerance. Peripheral immune tolerance is maintained, at least in part, by Regulatory T cells (Treg). Several studies have shown that either defects in the frequency or the suppressive capacity of Treg cells can contribute to the development of break of self-tolerance, and that in animal models of autoimmunity, adoptive transfer of Treg cells was able to stop disease process. Treg cells are known to be anergic in vitro to T cell receptor-induced (TCR) stimulation and this state correlates with their in vitro suppressive capacity. It has been reported that there are differences in the number of Treg cells in MS patients when compared with healthy controls. However there is also extensive evidence indicating a defect in the suppressive function of Treg cells from MS patients. In previous studies we showed that Treg cells produce an higher amount of leptin when compared with effector T cells and that leptin acts as a negative signal for the proliferation of Treg cells. In vitro leptin neutralization results in Treg cells proliferation. Although in last few years several studies have been performed to understand the molecular mechanism leading to autoimmune disorders development, there are no surrogate markers to predict the clinical progression of autoimmune diseases and the clinical response to the classical therapeutic regimes
Differential effects of α4ÎČ7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo
Objective: Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in inflammatory bowel diseases. We aimed to analyze the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4ÎČ7 and GPR15. Design: We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanized mouse model in DSS-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Results: Expression of GPR15 and α4ÎČ7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with ulcerative colitis (UC) as compared to CrohnÂŽs disease and controls. In vivo analysis in a humanized mouse model showed augmented gut homing of UC Treg cells as compared to controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4ÎČ7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. Conclusion: α4ÎČ7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic effector T cell expansion
Oral tolerance to cancer can be abrogated by T regulatory cell inhibition
Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue â JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut
Differential Responses of Human Regulatory T Cells (Treg) and Effector T Cells to Rapamycin
Background: The immunosuppressive drug rapamycin (RAPA) promotes the expansion of CD4+ CD25highFoxp3+ regulatory\ud
T cells via mechanisms that remain unknown. Here, we studied expansion, IL-2R-c chain signaling, survival pathways and resistance to apoptosis in human Treg responding to RAPA.\ud
Methodology/Principal Findings: CD4+CD25+ and CD4+CD25neg T cells were isolated from PBMC of normal controls (n = 21)\ud
using AutoMACS. These T cell subsets were cultured in the presence of anti-CD3/CD28 antibodies and 1000 IU/mL IL-2 for 3 to 6 weeks. RAPA (1â100 nM) was added to half of the cultures. After harvest, the cell phenotype, signaling via the PI3K/ mTOR and STAT pathways, expression of survival proteins and Annexin V binding were determined and compared to values obtained with freshly-separated CD4+CD25high and CD4+CD25neg T cells. Suppressor function was tested in co-cultures with autologous CFSE-labeled CD4+CD25neg or CD8+CD25neg T-cell responders. The frequency and suppressor activity of Treg were increased after culture of CD4+CD25+ T cells in the presence of 1â100 nM RAPA (p,0.001). RAPA-expanded Treg were largely CD4+CD25highFoxp3+ cells and were resistant to apoptosis, while CD4+CD25neg T cells were sensitive. Only Treg upregulated anti-apoptotic and down-regulated pro-apoptotic proteins. Treg expressed higher levels of the PTEN protein than CD4+CD25neg cells. Activated Treg6RAPA preferentially phosphorylated STAT5 and STAT3 and did not utilize the PI3K/ mTOR pathway.\ud
Conclusions/Significance: RAPA favors Treg expansion and survival by differentially regulating signaling, proliferation and sensitivity to apoptosis of human effector T cells and Treg after TCR/IL-2 activation
A Multilevel Property Hedonic Approach to Valuing Parks and Open Space
Many of the benefits that are generated by the natural environment are external to normal market transactions and are consequently undervalued and under-provisioned even though they substantially contribute to human welfare. One approach to valuing certain environmental goods and services is through a regression technique known as the property hedonic model. This model considers a property as a bundle of attributes where the total price of the property is decomposed into marginal, implicit prices for property-specific attributes, the context or neighborhood in which a property resides and access to environmental amenities. The goal of this dissertation research is to estimate the value of proximity to the environmental amenities of parks and open spaces using a property hedonic model for the City of Baltimore and suburban areas of Baltimore County. While the property hedonic model has been commonly used to value environmental benefits, few of these studies have distinguished the spatial scales of neighborhood characteristics from the property-specific characteristics within a regression model. In this research, a multilevel modeling approach to the typical property hedonic model was used to model the effects of attributes at different spatial scales. This approach also allowed the effect of environmental attributes to vary across geographic space and interact with attributes across spatial scales. Such methods provide a more realistic accounting of the dynamic spatial variation of the value of environmental goods and services. For parks in the City of Baltimore, the results of valuing proximity to parks showed a spatial dynamic not often captured in property hedonics. The overall fixed effect for distance to park was negative but insignificant. When allowed to vary by block group, the random effect for this variable indicated that only two-thirds of the 401 neighborhoods positively valued increased proximity to parks. No interactions were found to be significant for the entire study. However, for the population of block groups whose properties did positively value proximity to parks, the results of interactions with neighborhood and park characteristics showed that smaller and more open parks were valued higher than larger and more wooded parks. A high population density also increased the value for a property in close proximity to a park. Finally, properties with smaller yards placed a higher value on proximity to parks than those properties with larger yards, indicating a substitution effect. For open space in Baltimore County, the results indicated that while higher proportions of privately-owned open space surrounding a property increased the value of that property, open space that was publicly-accessible was not significantly valued. Privately-owned open space that was potentially developable was less than half the value of the positive effect of private, open space under conservation easements or other development restrictions
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Targeting the CBM complex causes Treg cells to prime tumours for immune checkpoint therapy.
Solid tumours are infiltrated by effector T cells with the potential to control or reject them, as well as by regulatory T (Treg) cells that restrict the function of effector T cells and thereby promote tumour growth1. The anti-tumour activity of effector T cells can be therapeutically unleashed, and is now being exploited for the treatment of some forms of human cancer. However, weak tumour-associated inflammatory responses and the immune-suppressive function of Treg cells remain major hurdles to broader effectiveness of tumour immunotherapy2. Here we show that, after disruption of the CARMA1-BCL10-MALT1 (CBM) signalosome complex, most tumour-infiltrating Treg cells produce IFNγ, resulting in stunted tumour growth. Notably, genetic deletion of both or even just one allele of CARMA1 (also known as Card11) in only a fraction of Treg cells-which avoided systemic autoimmunity-was sufficient to produce this anti-tumour effect, showing that it is not the mere loss of suppressive function but the gain of effector activity by Treg cells that initiates tumour control. The production of IFNγ by Treg cells was accompanied by activation of macrophages and upregulation of class I molecules of the major histocompatibility complex on tumour cells. However, tumour cells also upregulated the expression of PD-L1, which indicates activation of adaptive immune resistance3. Consequently, blockade of PD-1 together with CARMA1 deletion caused rejection of tumours that otherwise do not respond to anti-PD-1 monotherapy. This effect was reproduced by pharmacological inhibition of the CBM protein MALT1. Our results demonstrate that partial disruption of the CBM complex and induction of IFNγ secretion in the preferentially self-reactive Treg cell pool does not cause systemic autoimmunity but is sufficient to prime the tumour environment for successful immune checkpoint therapy
Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion.
Different functions have been attributed to natural regulatory CD4+CD25+FOXP+ (Treg) cells during malaria infection. Herein, we assessed the role for Treg cells during infections with lethal (DS) and non-lethal (DK) Plasmodium chabaudi adami parasites, comparing the levels of parasitemia, inflammation and anaemia. Independent of parasite virulence, the population of splenic Treg cells expanded during infection, and the absolute numbers of activated CD69+ Treg cells were higher in DS-infected mice. In vivo depletion of CD25+ T cells, which eliminated 80% of CD4+FOXP3+CD25+ T cells and 60â70% of CD4+FOXP3+ T cells, significantly decreased the number of CD69+ Treg cells in mice with lethal malaria. As a result, higher parasite burden and morbidity were measured in the latter, whereas the kinetics of infection with non-lethal parasites remained unaffected. In the absence of Treg cells, parasite-specific IFN-Îł responses by CD4+ T cells increased significantly, both in mice with lethal and non-lethal infections, whereas IL-2 production was only stimulated in mice with non-lethal malaria. Following the depletion of CD25+ T cells, the production of IL-10 by CD90â cells was also enhanced in infected mice. Interestingly, a potent induction of TNF- and IFN-Îł production by CD4+ and CD90â lymphocytes was measured in DS-infected mice, which also suffered severe anaemia earlier than non-depleted infected controls. Taken together, our data suggest that the expansion and activation of natural Treg cells represent a counter-regulatory response to the overwhelming inflammation associated with lethal P.c. adami. This response to infection involves TH1 lymphocytes as well as cells from the innate immune system
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