bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of T‐cell epitopes on U1A protein in MRL/lpr mice: double‐negative T cells are the major responsive cells
Authors: Yang Mei‐Hui , Suen Jau‐Ling , Li Shiao‐Lan , Chiang Bor‐Luen 
Published: May 2005

SummarySystemic lupus erythematosus (SLE) is characterized by the existence of a heterogeneous group of autoantibodies such as anti‐DNA, chromatin, histone, and ribonucleoprotein antibodies (Abs). Although the B‐cell antigenic determinants have been well characterized, very limited data about the T‐cell epitopes of self‐antigen (Ag) have been reported. In the present study, we analysed auto‐T‐cell epitopes using bone marrow‐derived dendritic cells (BM‐DCs) pulsed with murine U1A (mU1A) protein capable of activating autoreactive T cells from unprimed MRL/lpr mice in vitro. The data suggested that there are at least four T‐cell epitopes on the U1A protein, U1A31−50, U1A61−80, U1A201−220 and U1A271−287, and U1A31−50 had the most significant T‐cell proliferative response. In addition, the main responsive T cells are the CD4− CD8− double‐negative subgroup of T cells. Furthermore, we also demonstrated that the activation of double‐negative T cells is major histocompatibility complex class II restricted. The study here provides information on T‐cell epitope analysis of the U1A antigen using BM‐DCs as the effective antigen‐presenting cells.
Synergistic antibody induction by antigen–CD40 ligand fusion protein as improved immunogen
Authors: Li Wei 
Published: May 2005

SummaryFull scale B‐cell activation requires not only B‐cell receptor (BCR) engagement with antigen, but also costimulatory signals provided by T helper cells through the CD40–CD40 ligand (CD40L) interaction. It is hypothesized that a fusion protein of an antigen and soluble CD40L (CD40LT) would selectively target the costimulation to antigen‐specific B cells, leading to synergy in the antibody response. This hypothesis was investigated by fusing green fluorescence protein (GFP), a generic antigen, with mouse CD40LT. Studies revealed that immunization in mice with the plasmid encoding GFP–CD40LT fusion protein led to synergistic induction of GFP‐specific antibodies, while control plasmid(s) for GFP, CD40LT, or GFP plus CD40LT did not. Immunization with a single dose of the fusion protein also provoked a vigorous GFP‐specific immunoglobulin G1 antibody response, but not other antibody isotypes. These results suggest that GFP–CD40LT fusion protein induces a GFP‐specific B‐cell activation and antibody response in an antigen‐guided fashion. The potential application of this novel strategy in vaccine development is discussed.
The negative regulatory function of the lymphocyte‐activation gene‐3 co‐receptor (CD223) on human T cells
Authors: Maçon‐Lemaître Laëtitia , Triebel Frédéric 
Published: May 2005

SummaryAccumulating evidence indicates that the CD4 homologue lymphocyte activation gene‐3 (LAG‐3) plays a down‐regulatory role on T‐cell responses. However, the role of LAG‐3/major histocompatibility complex (MHC) class II interactions on primary human T‐cell responses, as well as the mechanism by which down‐regulation occurs, are not clear. Here, we show that LAG‐3 colocalized with CD3, CD4 or CD8 in areas of cholesterol‐rich raft aggregation during this primary response, as well as in the clustered raft region formed between T cells and antibody‐coated beads. Addition of a blocking LAG‐3‐specific monoclonal antibody to both CD4 and CD8 primary resting T cells activated under conditions of antigen‐presenting cell‐driven stimulation and low antigen concentrations augments CD69 activation antigen expression, T‐cell expansion and T helper 1 (Th1, but not Th2) cytokine production. Blocking LAG‐3/MHC class II interactions leads to an increase in the number of cells entering division at these low concentrations of antigen and to more rounds of divisions with an accumulation of cells in the S‐phase of the cell cycle. These results indicate that LAG‐3 signalling inhibits early events in primary activation of human CD4 and CD8 T cells and further support a role for LAG‐3 signalling in regulating the expansion of activated effector or memory T cells, either directly or indirectly through Treg suppressor activity.
Differential expression of regulator of G‐protein signalling transcripts and in vivo migration of CD4+ naïve and regulatory T cells
Authors: Agenès Fabien , Bosco Nabil , Mascarell Laurent , Fritah Sabrina , Ceredig Rod 
Published: May 2005

SummaryThe immune response of T lymphocytes to pathogens is initiated in draining secondary lymphoid organs, and activated cells then migrate to the site of infection. Thus, control of naïve and regulatory CD4+ T‐cell migration is crucial; however, it is poorly understood in physiological and pathological conditions. We found that CD4+ subpopulations displayed characteristic regulator of G‐protein signalling (RGS) gene expression profiles. Regulatory T cells express higher levels of RGS1, RGS9 and RGS16 than naïve cells. These genes are up‐regulated upon cell activation and their level of expression correlates with in vivo cell migration. Using parabiosis, we showed that regulatory T lymphocytes migrate less than naïve T cells and that migrant naïve T cells express even lower RGS levels than their static counterparts. Our results show an inverse correlation between the capacity to migrate and the levels of RGS1, RGS9 and RGS16 for both naïve and regulatory T cells. Taken together, these results suggest a role for RGS molecules in chemokine‐induced lymphocyte migration and demonstrate the peculiarity of regulatory T cells in terms of phenotype and migration ability, providing new insights into their function.
Delineation of multiple subpopulations of natural killer cells in rhesus macaques
Authors: Webster Ramothea L. , Johnson R. Paul 
Published: May 2005

SummaryNatural killer (NK) cells in rhesus macaques have been variably defined as CD3− CD16+ or CD3− CD8+, although only limited efforts have been made to validate these definitions rigorously. To better understand the role of NK cells in macaque disease models, we undertook a multiparameter analysis of macaque NK cells employing four‐colour flow cytometry and a panel of lineage‐specific and non‐lineage‐specific lymphocyte markers. Using this approach, we identified two distinct populations of candidate NK cells: a major CD8bright CD16+ population and a minor CD8bright CD16− population. Further analysis of the major and minor NK cell populations revealed the expression of multiple markers characteristic of NK cells, including CD2, CD7, CD16, CD161, NKG2A and granzyme B. In addition, a CD56+ subset of cells within the minor rhesus NK population was identified which expressed chemokine and lymph node homing receptors similar to those expressed by the CD56bright NK cell population identified in humans. Cytolytic assays confirmed that the phenotypically defined rhesus NK cells lysed NK‐susceptible target cells. Our observations support the existence of several distinct subpopulations of rhesus macaque NK cells, which have significant phenotypic and functional similarities to their human counterparts. These improved immunophenotypic definitions of macaque NK cells should facilitate future analysis of innate immune responses in rhesus macaques and the role of NK cells in AIDS pathogenesis in Simian immunodeficiency virus (SIV)‐infected macaques.
Impaired B cell responses to orally administered antigens in lamina propria but not Peyer's patches of Gαi2‐deficient mice prior to colitis
Authors: Öhman Lena , Åström Rolf‐Göran , Hultgren Hörnquist Elisabeth 
Published: May 2005

SummaryDespite numerous studies on the intestinal immune system in patients with inflammatory bowel disease (IBD) and animal models of IBD, very little is known about the immune reactivity of mucosal lymphocytes following oral immunizations under these circumstances. The reactivity of Peyer's patch (PP) and lamina propria (LP) T and B lymphocytes in inhibitory G‐protein α2 subunit‐deficient (Gαi2–/–) mice developing an IBD resembling ulcerative colitis was investigated following repeated oral immunizations with keyhole limpet haemocyanin (KLH), together with the adjuvant cholera toxin, prior to colitis. The antigen‐specific B‐cell response in the LP of both the small and the large intestines was significantly reduced in Gαi2–/– as compared to wild‐type mice. In contrast, the frequency of KLH‐specific immunoglobulin (Ig)‐producing cells in the PP did not differ between Gαi2–/– and wild‐type mice, whereas the total frequency of Ig‐producing cells as well as the frequency of enteric flora‐specific Ig‐producing cells in the PP was significantly increased in Gαi2–/– as compared to wild‐type mice. Analysis of T cell responses following restimulation ex vivo with KLH revealed a dramatic increase in the production of interferon‐γ in mesenteric lymph node, PP and LP lymphocytes from Gαi2‐deficient as compared to wild‐type mice, together with decreased production of interleukin‐10 in all locations except the PP.
The Vγ2/Vδ2 T‐cell repertoire in Macaca fascicularis: functional responses to phosphoantigen stimulation by the Vγ2/Jγ1.2 subset
Authors: Cairo Cristiana , Propp Nadia , Hebbeler Andrew M. , Colizzi Vittorio , Pauza C. David 
Published: May 2005

SummaryCirculating Vγ2/Vδ2 T cells in human and non‐human primates respond to small molecular weight non‐peptidic phosphoantigens in a major histocompatibility complex (MHC)‐unrestricted manner. These responses are encoded by the Vγ2/Jγ1.2 chain of the T‐cell receptor and are positively selected during early development to create a biased repertoire in adults. We characterized the Vγ2 chain in cynomolgus macaques (Macaca fascicularis) to develop a non‐human primate model for studying the effects of infection and therapy on the circulating Vγ2/Vδ2 T‐cell subset. The cynomolgus macaque Vγ2 chain was highly homologous to the Vγ2 chain from human beings and rhesus macaques (Macaca mulatta), though we noted conserved substitutions in critical residues within the CDR3 for both macaque species. Despite these substitutions, Vγ2/Vδ2+ T cells from cynomolgus monkeys exhibited polyclonal responses to two different phosphoantigens. Proliferative responses were observed with both isopentenylpyrophosphate and alendronate, but stronger interferon‐γ secretory responses were observed with isopentenylpyrophosphate. In vitro stimulation and expansion led to selective outgrowth of the Vγ2/Jγ1.2 subset, with a marked shift in the Vγ2 spectratype. As a result of the less biased starting repertoire for Vγ2, the cynomolgus macaque constitutes a sensitive model for examining the effects of in vitro or in vivo treatments on the Vγ2/Vδ2 T‐cell population. Our studies establish the value of cynomolgus macaques as a model for Vγ2/Vδ2 T‐cell responses to non‐peptidic antigens, and further evidence the remarkable evolutionary conservation of this unusual, phosphoantigen‐responsive T‐cell subset that is found only in primate species.
Building better T‐cell‐inducing malaria vaccines
Authors: Todryk Stephen M. , Walther Michael 
Published: May 2005

SummarySince malaria continues to account for millions of deaths annually in endemic regions, the development of an effective vaccine remains highly desirable. The life cycle of malaria poses a number of challenges to the immune response since phases of the cycle express varying antigen profiles and have different locations, thus requiring differing antigenic targets and effector mechanisms. To confer sterile immunity, a vaccine would have to target the pre‐erythrocytic stages of infection. Since at this stage the parasite is hidden within liver cells, the host defence predominantly requires cell‐mediated immunity, chiefly T cells, to eliminate infected hepatocytes. The development of such vaccines has progressed from irradiated sporozoites, through recombinant proteins, to recombinant DNA and viral vectors. Some of the experimental vaccination regimens that explore various combinations of vaccines for priming and boosting, together with numbers of vaccinations, interval between them, and the vaccination site, are revealing strong immunogenicity and evidence of efficacy in human challenge studies and in field trials. Such approaches should lead to deployable vaccines that protect against malarial disease.
Comparative cell signalling activity of ultrapure recombinant chaperonin 60 proteins from prokaryotes and eukaryotes
Authors: Maguire Maria , Poole Stephen , Coates Anthony R. M. , Tormay Peter , Wheeler‐Jones Caroline , Henderson Brian 
Published: May 2005

SummaryHeat‐shock protein (hsp)60/chaperonin 60 is a potent immunogen which has recently been claimed to have cell‐signalling actions upon myeloid and vascular endothelial cells. The literature is controversial with different chaperonin 60 proteins producing different patterns of cellular activation and the ever‐present criticism that activity is the result of bacterial contaminants. To clarify the situation we have cloned, expressed and purified to homogeneity the chaperonin 60 proteins from Chlamydia pneumoniae, Helicobacter pylori and the human mitochondrion. These highly purified proteins were compared for their ability to stimulate human peripheral blood mononuclear cell (PBMC) cytokine synthesis and vascular endothelial cell adhesion protein expression. In spite of their significant sequence homology, the H. pylori protein was the most potent PBMC activator with the human protein the least potent. PBMC activation by C. pneumoniae and human, but not H. pylori, chaperonin 60 was blocked by antibody neutralization of Toll‐like receptor‐4. The C. pneumoniae chaperonin 60 was the most potent endothelial cell activator, with the human protein being significantly less active than bacterial chaperonin 60 proteins. These results have implications for the role of chaperonin 60 proteins as pathological factors in autoimmune and cardiovascular disease, and raise the possibility that each of these proteins may result in different pathological effects in such diseases.
Functional characterization of T cells in abdominal aortic aneurysms
Authors: Forester Nerys D. , Cruickshank Sheena M. , Scott D. Julian A. , Carding Simon R. 
Published: May 2005

SummaryAbdominal aortic aneurysms (AAA) exhibit features of a chronic inflammatory disorder. The functional attributes of the T cells in AAA tissue are unclear, with little quantitative or functional data. Using a novel, non‐enzymatic method to isolate viable cells from AAA tissue, functional properties of AAA T cells were investigated for the first time. Composition and phenotype of AAA T cells was determined by flow cytometry and verified by immunohistochemistry. Tissue mononuclear cells (MNCs) were cultured in the presence of T‐cell mitogens, and cell cycle analysis and cytokine production assessed. Typical cell yield was 4·5 × 106 cells per gram of AAA tissue. The majority (58·1 ± 5·3%) of haematopoietic (CD45+) cells recovered were CD3+ T cells, B cells comprised 41·1 ± 5·7%, natural killer cells 7·3 ± 2·5%, and macrophages 2%. Freshly isolated T cells were in resting (G1) state, with 25% expressing the activation‐associated cell surface antigens major histocompatibility complex II and CD25. When stimulated in vitro, a significant proportion entered S and G2 phase of the cell cycle, up‐regulated CD25, and secreted tumour necrosis factor‐α, interferon‐γ, interleukin (IL)‐5 and IL‐6. Despite patient differences, the composition of the AAA inflammatory infiltrate was remarkably consistent, and when re‐stimulated ex‐vivo T cells produced a stereotypical cytokine response, consistent with the hypothesis that AAA T cells can promote tissue inflammation by secretion of proinflammatory cytokines, and in addition provide signals for B‐cell help.
Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria
Authors: Macpherson Andrew J. , Geuking Markus B. , McCoy Kathy D. 
Published: May 2005

SummaryAnimals contain an enormous load of non‐pathogenic bacteria in the lower intestine, which exploit an environment with a stable temperature and abundant carbon sources. Our load of bacteria outnumbers our own cells. In order to survive with such a high number of organisms in very close proximity to host tissues the intestinal mucosa and its immune system is highly adapted. Mucosal immune responses are induced by small numbers of live commensal organisms penetrating the Peyer's patches and persisting in dendritic cells (DC). These DC can induce immunoglobulin A+ (IgA+) B cells, which recirculate through the lymph and bloodstream to populate the lamina propria and secrete protective IgA. Because DC loaded with commensal bacteria do not penetrate further than the mesenteric lymph nodes, immune induction to commensals is confined to the mucosa, allowing strong mucosal immune responses to be induced whilst the systemic immune system remains relatively ignorant of these organisms.
Motivational interviewing to promote physical activity for people with chronic heart failure
Authors: Brodie David A. , Inoue Alison 
Published: May 2005

Aim.  This paper reports a study comparing, over a 5‐month period, two different methods of increasing physical activity: a traditional exercise programme and one based on motivational interviewing.Background.  Chronic heart failure is associated with poor quality of life that can be improved by increased physical activity. Patients who are directed to engage in physical activity have a record of low compliance.Method.  Sixty older aged heart failure patients were randomly assigned to standard care, motivational interviewing or both treatments. The primary outcome was physical activity (kcal/kg/day), with the 6‐minute walk test as a secondary outcome.Findings.  At entry, no significant differences were observed between the three groups. Following treatment, the ‘motivational interviewing’ and ‘both treatments’ groups reported an increase in their level and type of activities, whereas the ‘standard care’ group did not. All groups significantly increased their 6‐minute walk distance.Conclusions.  Motivational interviewing, which incorporates established behaviour change principles and a flexible approach to promotion of activity, increases reported physical activity in older patients with heart failure over a short period. In terms of level and type of activity, this approach gives a better outcome than standard care, and nurses should explore alternative strategies to promote health in this population.
Working with girls living on the streets in East Africa: professionals’ experiences
Authors: Savenstedt Stefan , Häggstrom Terttu 
Published: May 2005

Aim. This paper reports a study elucidating the meaning of caring for girls of the street, as experienced by female staff members working with street children in Eastern Africa.Background. The phenomenon of children living on the streets is a global and escalating problem, and girls are presumed to be especially vulnerable. In East Africa, the traditional extended family system is rapidly breaking down and traditional gender values seem to remain. This was the context for investigating female carers’ experience of caring for girls.Method. Interviews were conducted with 37 project staff members working with children living on the streets in the framework of non‐governmental organizations in Kenya, Uganda and Tanzania between 1997 and 1998. Transcribed text from female interviewees (n = 13) working with girls of the street was analysed using a phenomenological‐hermeneutic approach.Findings. The meaning of caring for girls of the street for female professional carers in East Africa was comprehensively understood as counselling the girls to integrate the past of their adverse life stories with their present identity. Counselling meant conveying visions for a possible re‐direction of the life stories, from being a girl of the street into being an accepted family girl. Caring in this context meant being squeezed between ethical demands and gender values. Experiencing frustration and powerlessness was related to gender structures in society, having to fight the grip of street culture, and a lack of professional tools. Hope and satisfaction were related to success in changing the course of life stories of girls and to seeing possibilities for contributing to empowerment of girls and community members.Conclusions. Gender issues are critical to care provided to girls of the street. Carers felt that they lacked relevant knowledge and support. Ethical aspects and gender issues in relation to professional care for vulnerable girls ought to be addressed in nursing education and practice, not only for developing countries, but also as a matter of global interest.
First‐time mothers: social support and confidence in infant care
Authors: Leahy Warren Patricia 
Published: May 2005

Aim. This paper reports a study whose primary aim was to explore the relationship between social support for first‐time mothers and their confidence in infant care practices. A secondary aim was to identify their sources of support in the postnatal period.Background. Policy documents emphasize the importance of support for new mothers in the postnatal period in caring for their infants. Nurses/midwives require a working knowledge of how social support influences maternal confidence in infant care practices, specifically during the first 6 weeks postdelivery.Methods. A descriptive, correlational design was used. A 28 item questionnaire was designed to measure social support in the specific context of first‐time motherhood and confidence in infant care practices. Content validity was sought and the instrument demonstrated reliability using Cronbach's alpha. A convenience sample of 135 first‐time mothers was recruited and 74% completed questionnaires at 6 weeks after birth. Data were collected in 2000.Results. Appraisal support had a statistically significant moderate relationship with confidence in infant care practices (r = 0·4,P < 0·01). Informational support had a weaker but statistically significant relationship (r = 0·2,P < 0·05). Respondents’ primary sources of appraisal support were husbands/partners and their own mothers. Public health nurses and mothers were primary sources of informational support.Conclusions. First‐time mothers’ husbands/partners need to become active participants in antenatal and postnatal care. Interdisciplinary educational programmes need to be developed so that public health nurses and midwives work collaboratively in facilitating social support for first‐time mothers in caring for their infants. Curricula for public health nurses and midwives need to be evidenced‐based with respect to social support.