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- Brodin, P, et al.
(författare)
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The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 113:11, s. 2434-2441
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I. If self-MHC is down-regulated or absent, lack of inhibition triggers “missing self” killing. NK cells developing in the absence of MHC class I are hypo-responsive, demonstrating that MHC class I molecules are required for NK-cell education. Here, we show that the number and the type of MHC class I alleles that are present during NK-cell education quantitatively determine the frequency of responding NK cells, the number of effector functions in individual NK cells, and the amount of interferon-γ production in NK cells of specific Ly49 subsets. A relationship between the extent of inhibitory signals during education and functional responsiveness was corroborated by an enhanced probability of NK cells expressing more than one inhibitory receptor for a single host self–MHC class I allele to degranulate after activation. Our data suggest that the capacity of an individual NK cell to respond to stimulation is quantitatively controlled by the extent of inhibitory signals that are received from MHC class I molecules during NK-cell education.
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- Lakshmikanth, T, et al.
(författare)
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An assay for immunological health
- 2017
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Ingår i: SCANDINAVIAN JOURNAL OF IMMUNOLOGY. - 0300-9475. ; 86:4, s. 300-301
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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- Lakshmikanth, T., et al.
(författare)
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Human Immune System Variation during 1 Year
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal cum. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.
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- Lakshmikanth, T, et al.
(författare)
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Systems-Level Immune Monitoring by Mass Cytometry
- 2019
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Ingår i: Methods in molecular biology (Clifton, N.J.). - New York, NY : Springer New York. - 1940-6029. ; 1913, s. 33-48
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Tidskriftsartikel (refereegranskat)
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- Petkov, S, et al.
(författare)
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High CD45 expression of CD8+ and CD4+ T cells correlates with the size of HIV-1 reservoir in blood
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 20425-
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Tidskriftsartikel (refereegranskat)abstract
- Using mass cytometry, we investigated the expression of 28 markers on CD8+ and CD4+ T cells from HIV-1 infected patients with a variable size of HIV-1 reservoir defined as high (HR) and low (LR) reservoir; we aimed at identifying phenotypic associations of T cells with size of HIV-1 reservoir. We showed that the frequency of CD45+ CD8+ and CD4+ T cells was directly proportional to the size of HIV-1 reservoir; HR patients had a significantly larger frequency of blood CD45high T cells and higher CD45 expression on both CD8+ and CD4+ T cells. CD45 is a receptor-type protein tyrosine phosphatase essential in TCR signaling. Functional and phenotypical analysis of CD45high cells revealed that they express activation and proliferation markers (CD38 + HLA-DR + and Ki-67) and produce cytokines upon in vitro activation. CD45high T cells also expressed high levels of immune check-point PD-1. Our results link CD45 expression on T cells to HIV-1 reservoir; PD-1 expression on CD45high T cells may contribute to their exhaustion.
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- Silva, CS, et al.
(författare)
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High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 727300-
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Tidskriftsartikel (refereegranskat)abstract
- Upon infection withMycobacterium tuberculosis(Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and purified-protein derivate (PPD). At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both pro-inflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-γ. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.
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