| 1. |
- Nasi, Aikaterini, et al.
(författare)
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Dendritic cell response to HIV-1 is controlled by differentiation programs in the cells and strain-specific properties of the virus
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8:MAR
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC-HIV-1 interactions might be highly variable, shaped by endogenous features of the cells and diversity of the virus.
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| 2. |
- Tauriainen, Johanna, et al.
(författare)
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Single-cell characterization of in vitro migration and interaction dynamics of T cells expanded with IL-2 and IL-7
- 2015
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- T cells are pivotal in the immune defense against cancers and infectious agents. To mount an effector response against cancer cells, T cells need to migrate to the cancer-site, engage in contacts with cancer cells, and perform their effector functions. Adoptive T cell therapy is an effective strategy as treatment of complications such as relapse or opportunistic infections after hematopoietic stem cell transplantations. This requires a sufficient amount of cells that are able to expand and respond to tumor or viral antigens. The cytokines interleukin (IL)-2 and IL-7 drive T cell differentiation, proliferation, and survival and are commonly used to expand T cells ex vivo. Here, we have used microchip-based live-cell imaging to follow the migration of individual T cells, their interactions with allogeneic monocytes, cell division, and apoptosis for extended periods of time; something that cannot be achieved by commonly used methods. Our data indicate that cells grown in IL-7 + IL-2 had similar migration and contact dynamics as cells grown in IL-2 alone. However, the addition of IL-7 decreased cell death creating a more viable cell population, which should be beneficial when preparing cells for immunotherapy.
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| 3. |
- Wallin, Anders, 1950, et al.
(författare)
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Alzheimer's disease-subcortical vascular disease spectrum in a hospital-based setting: overview of results from the Gothenburg MCI and dementia studies.
- 2016
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 36:1, s. 95-113
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Forskningsöversikt (refereegranskat)abstract
- The ability to discriminate between Alzheimer's disease (AD), subcortical vascular disease, and other cognitive disorders is crucial for diagnostic purposes and clinical trial outcomes. Patients with primarily subcortical vascular disease are unlikely to benefit from treatments targeting the AD pathogenic mechanisms and vice versa. The Gothenburg mild cognitive impairment (MCI) and dementia studies are prospective, observational, single-center cohort studies suitable for both cross-sectional and longitudinal analysis that outline the cognitive profiles and biomarker characteristics of patients with AD, subcortical vascular disease, and other cognitive disorders. The studies, the first of which started in 1987, comprise inpatients with manifest dementia and patients seeking care for cognitive disorders at an outpatient memory clinic. This article gives an overview of the major published papers (neuropsychological, imaging/physiology, and neurochemical) of the studies including the ongoing Gothenburg MCI study. The main findings suggest that subcortical vascular disease with or without dementia exhibit a characteristic neuropsychological pattern of mental slowness and executive dysfunction and neurochemical deviations typical of white matter changes and disturbed blood-brain barrier function. Our findings may contribute to better healthcare for this underrecognized group of patients. The Gothenburg MCI study has also published papers on multimodal prediction of dementia, and cognitive reserve.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 July 2015; doi:10.1038/jcbfm.2015.148.
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| 4. |
- Wallin, Anders, 1950, et al.
(författare)
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The Gothenburg MCI study: design and distribution of Alzheimer's disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up.
- 2016
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 36:1, s. 114-131
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for increased nosological knowledge to enable rational trials in Alzheimer's disease (AD) and related disorders. The ongoing Gothenburg mild cognitive impairment (MCI) study is an attempt to conduct longitudinal in-depth phenotyping of patients with different forms and degrees of cognitive impairment using neuropsychological, neuroimaging, and neurochemical tools. Particular attention is paid to the interplay between AD and subcortical vascular disease, the latter representing a disease entity that may cause or contribute to cognitive impairment with an effect size that may be comparable to AD. Of 664 patients enrolled between 1999 and 2013, 195 were diagnosed with subjective cognitive impairment (SCI), 274 with mild cognitive impairment (MCI), and 195 with dementia, at baseline. Of the 195 (29%) patients with dementia at baseline, 81 (42%) had AD, 27 (14%) SVD, 41 (21%) mixed type dementia (=AD+SVD=MixD), and 46 (23%) other etiologies. After 6 years, 292 SCI/MCI patients were eligible for follow-up. Of these 292, 69 (24%) had converted to dementia (29 (42%) AD, 16 (23%) SVD, 15 (22%) MixD, 9 (13%) other etiologies). The study has shown that it is possible to identify not only AD but also incipient and manifest MixD/SVD in a memory clinic setting. These conditions should be taken into account in clinical trials.Journal of Cerebral Blood Flow & Metabolism advance online publication, 15 July 2015; doi:10.1038/jcbfm.2015.147.
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