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The pro-inflammatory and regulatory roles of T lymphocytes in atherosclerosis are well established but less is known about natural killer (NK) cells and natural killer T (NKT)-like cells. The effects of cardiovascular risk management on the phenotypes of these cells are unknown. To assess changes in NK cell and lymphocyte phenotypes and circulating inflammatory proteins in response to cardiovascular risk management in patients with carotid atherosclerosis. Fifty patients were included in a prospective clinical study. Measurements were at baseline and after 12 months of cardiovascular risk management. Circulating NK, NKT-like and T lymphocyte subpopulations were phenotyped by multi-colour flow cytometry. Proximity extension assay was performed for 176 plasma proteins associated with inflammation and cardiovascular disease. At 12 months there were significant reductions in LDL (P = 0.001) and blood pressure (P = 0.028). NK cells responded with a reduction in pro-inflammatory (NKG2C + ) cells (P = 0.0003), an increase in anti-inflammatory (NKG2A + ) cells (P = 0.032), and a reduction in terminally differentiated (CD57 + ) NK cells. NKT-like cells showed a similar decrease in terminally differentiated subpopulations (P = 0.000002). Subpopulations of T helper cells exhibited a significant reduction in central memory (P = 1.09 × 10 −8 ) and a significant increase in CD4 + naïve- (P = 0.0008) and effector memory T cells (P = 0.006). The protein analysis indicated that cardiovascular risk management affects proteins involved in the inflammatory NF-κB pathway. The consistent decrease in senescent phenotypes of NK, NKT-like and CD4 + cells with a concomitant increase in more naïve, phenotypes suggests a change towards a less pro-inflammatory lymphocyte profile in response to cardiovascular risk management. Trial registry name : CARotid MRI of Atherosclerosis (CARMA). ClinicalTrials.gov identifier NCT04835571 (08/04/2021). https://www.clinicaltrials.gov/study/NCT04835571 .

After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19. Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection. We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets. By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.

The hallmark of HIV-1 (HIV) infection is the progressive development of multicellular and systemic immune dysfunction, culminating in AIDS. Dendritic cells (DCs) play a pivotal role in HIV dissemination to CD4 + T cells, which are subsequently depleted by the virus leading to HIV disease progression. Type I interferons (IFNs) are critical for host defense during acute infection but contribute to chronic immune activation during the later stages of HIV disease. This persistent activation leads to immune cell exhaustion. HIV can activate type I IFN responses via several pathways, including the STING pathway, which is activated by, e.g., virus-derived oligonucleotides. Here, we investigated the underlying mechanisms creating HIV-mediated immune dysfunction and role of type I IFNs using a DC and T cell co-culture model. HIV exposure in the DC-T cell co-culture promoted the expansion of suppressive T cells with diminished proliferation and effector functions. The impairment required type I IFNs and subsequent IFNα/β receptor signaling, and our data indicate that this was initiated by HIV-derived ssDNA activation of IFI16/cGAS followed by STING signaling in the DCs. Targeting IFNAR1 with anifrolumab restored the immune functions of both DCs and T cells, as well as T cell proliferation and T cell effector functions, including their secretion of IL-2, IFNγ, and granzyme B. Our findings support that the immune impairments existing in untreated or antiretroviral therapy (ART) treated HIV-infected individuals are mediated, if not fully in part by type I IFN’s negative effect on DC and T cells. Therapeutics targeting IFNα/β receptors, such as anifrolumab, hold potential as combination treatment alongside ART, to achieve a more complete immune restoration and contribute to improved quality of life among people living with HIV.

Background The immune response to SARS-CoV-2 virus, the cause of COVID-19, is complex. Antibody mediated responses are important for viral clearance but may also drive hyperinflammation in severe COVID-19. We present a case of an individual with a genetic inability to produce antibodies and severe COVID-19, receiving no other specific anti-viral treatment than convalescent COVID-19 plasma, illustrating that hyperinflammation can occur in the absence of a humoral anti-viral response. In addition, the case illustrates that the assessment of SARS-CoV-2 T cell responses can facilitate clinical decision making in patients with COVID-19 and weak or absent humoral immune responses. Case presentation A male with X-linked agammaglobulinemia on regular immunoglobulin replacement therapy, hospitalized for 35 days due to severe COVID-19. Systemic inflammatory parameters were highly elevated. After treatment with convalescent COVID-19 plasma he became afebrile and the fatigue diminished. He was discharged on day 42 and nasopharyngeal SARS-CoV-2 PCR eventually was negative on day 49. Evidence of SARS-CoV-2 specific T cells prior to administration of plasma therapy suggested that antibodies were crucial for viral clearance. Regular assessment showed robust and persistent SARS-CoV-2 specific T-cell responses after recovery suggested that prophylactic administration of convalescent COVID-19 plasma was unnecessary. Conclusion Assessment of SARS-CoV-2T-cell responses can facilitate the clinical management of COVID-19 patients with humoral immunodeficiencies.

PurposeCommon variable immunodeficiency (CVID) is a primary antibody deficiency that commonly manifests as recurrent infections. Many CVID patients also suffer from immune dysregulation, an inflammatory condition characterized by polyclonal lymphocytic tissue infiltration and associated with increased morbidity and mortality. The genetic cause is unknown in most CVID patients and epigenetic alterations may contribute to the broad range of clinical manifestations. MicroRNAs are small non-coding RNAs that are involved in epigenetic modulation and may contribute to the clinical phenotype in CVID.MethodsHere, we determined the circulating microRNAome and plasma inflammatory proteins of a cohort of CVID patients with various levels of immune dysregulation and compared them to healthy controls. A set of deregulated microRNAs was validated by qPCR and correlated to inflammatory proteins and clinical findings.ResultsLevels of microRNA-34a correlated with 11 proteins such as CXCL9, TNF, and IL10, which were predicted to be biologically connected. Moreover, there was a negative correlation between mir-34 levels and the number of naïve CD4 T cells in CVID.ConclusionCollectively, our data show that microRNAs correlate with the inflammatory response in CVID. Further investigations are needed to elucidate the role of miRNAs in the development of CVID-related immune dysregulation.

In public discourse, the social inclusion of migrants is often regarded as a challenge demanding migrants to increase their engagement in adapting to the new host country. Such imaginaries commonly declare migrants as being unwilling to acquire language skills and specific cultural values. In parallel, formal education is often proposed as the single most important remedy to inclusion, which generally solely implies labor market participation. However, there is a range of other, often neglected, practices that migrants themselves regard as important for their social inclusion in society. This article aims to analyze what practices are assigned meaning by newly arrived migrants in Sweden on their path toward social inclusion in the country. This is a longitudinal interview study with 19 newly arrived adult migrants that were interviewed on two occasions, three years apart. Drawing on a sociocultural perspective, we understand social inclusion as an ongoing process by which individuals become members of different communities. The result shows that important for social inclusion is access to valuable relationships and close social ties. These relations are important in all communities in which the migrants participate. The analysis illustrates three different communities, outside of formal education and employment, that migrants ascribe meaning to concerning language learning and social inclusion. These communities are sports, internships, and civil society engagements. Through its longitudinal design, this study also illustrates how migrants’ narratives and their meanings shift with time and how migrants relate to these communities over time.

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8 + TEMRA and exhausted CD57 + CD8 + T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69 + CD4 + T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

It is argued that the use of high-fidelity simulators is educationally effective, since students are able to work more independently and can better control their learning. Therefore, simulations can be used as a teaching method to facilitate and ease teachers’ work situations. This raises questions as to whether teachers’ professional bodies are a bounded physicality, or whether we can understand teachers’ professional bodies in practice in terms of enactments? This article analyses and discusses the enactment of VET teachers’ professional bodies in the context of vocational and simulation-based training. The empirical material is based on ethnographic observations in three classes in two different vocational education programmes at two upper secondary schools in Sweden. Three different cases are presented and analysed as examples of how VET teachers’ professional bodies are enacted. Guided by a practice theory perspective (Schatzki, T. R. Social practices: a Wittgensteinian approach to human activity and the social (1996), Schatzki, T. R. The site of the social: A philosophical account of the constitution of social life and change (2002), Schatzki, T. R. & Natter, W. Sociocultural bodies, bodies sociopolitical. In T. R.Schatzki & W. Natter (Eds.), The social and political body (1996), the study shows that VET teachers’ professional bodies are enacted in multiples, distributed, and delegated in an interplay between the teachers, the students, the simulator, and its material set-up. In these enactments of professional bodies, VET teachers embody both a teacher identity and a previous vocational identity, which they perform simultaneously depending on the educational situation.

This article is centred on the tendency to align education for newly arrived students with migration policy. Drawing on an in-depth analysis of interviews with four adult migrant students, we aim to investigate how the participants' experiences of studying and how they imagine their future intersect with their immigration status. The interviews were conducted when they were first studying a language introduction programme, and then three years later. We focus on the participants' narratives about transitions within the education system and later into the labour market. Using Sara Ahmed's approach to the orientation of subjects in time and space, the analysis shows that all students expressed a desire to \"be in line,\" meaning finishing their studies and finding employment. Students with temporary and conditional residence permits were directed towards specific vocational tracks and sectors of the labour market. Migrant students are a heterogenous group and, based on the findings presented, we argue that immigration status constitutes a crucial part of this heterogeneity, influencing how students imagine their future in a new society.

This paper explores the development of professional identity as a relationship between professional and personal aspects of life. The focus is on student and novice professional psychologists’ and political scientists’ processes of professional identity formation in their transition from higher education to working life. Drawing on Wenger’s theory of nexus of multimembership ( 1998 ), the findings indicate that professional identity is a dynamic relationship between different life spheres rather than an isolated phenomenon only taking place at the university or in the work context. The analysis yielded three different forms of professional identity, non-differentiated identity, compartmentalised identity and integrated identity, which exemplify different negotiated relationships between professional, personal and private life spheres. The findings show that these three forms of professional identities are sequential, from an individual focus to more relational and integrated ways of reasoning about one’s profession. It is through the negotiations between personal and socially derived imperatives that identity formation progresses throughout working lives.