Immune-Monitoring
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Immune-Monitoring
Identifying antigen-specific immune cells in infection, neoplasia and auto-immunity
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The regulatory B cell compartment expands transiently during childhood and is contracted in children with autoimmunity - Kalampokis - Arthritis & Rheumatology - Wiley Online Library

The regulatory B cell compartment expands transiently during childhood and is contracted in children with autoimmunity - Kalampokis - Arthritis & Rheumatology - Wiley Online Library | Immune-Monitoring | Scoop.it
The phenotype and numbers of blood B10 cells were examined in healthy individuals and children with autoimmunity by flow cytometry. B10 cell function was assessed by measuring the effect of B cell-derived IL-10 on CD4+ T cell interferon-gamma (IFN-γ) expression. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA).B10 cells, a functionally-defined subset with variable surface phenotype reflective of overall B cell development, transiently expand during childhood. The decreased B10 cell frequencies and numbers in children with autoimmunity may be partially explained by the differential regulation of B10 cell development by IFN-γ and IL-21 and alterations in serum cytokine levels.
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Ex vivo expanded regulatory T cells CD4+CD25+FoxP3+CD127Low develop strong immunosuppressive activity in patients with remitting-relapsing multiple sclerosis

Ex vivo expanded regulatory T cells CD4+CD25+FoxP3+CD127Low develop strong immunosuppressive activity in patients with remitting-relapsing multiple sclerosis | Immune-Monitoring | Scoop.it
Multiple sclerosis (MS) is an autoimmune disease characterized by defect in regulatory function of CD4+CD25+ T cells. We demonstrated difference in proportion of regulatory T cells CD4+CD25+FoxP3+CD127low (Tregs) within the same patients’ relapse and remission. Proportion of peripheral Tregs (pTregs) dropped almost two times in the relapse compare to remission. Levels of pTregs in patients’ remission were lower than in healthy donors. Suppressive ability of pTregs was decreased in MS patients compared to healthy donors. Injections of expanded ex vivo autologous Tregs (eTregs) could be helpful in bringing up the level of Tregs in patients’ blood. We developed a simple method for ex vivo expansion of autologous Tregs within a short period of time. The final pool of cells consisted of 90-95% eTregs. When we started the culture with 10-20 × 106 CD4+ T cells, we yield 300-400 × 106 eTregs in a week. Expression of FoxP3 and Helios was calculated by two methods. Expanded ex vivo patients’ and donors’ Tregs were characterized by increased from three to five times expression of FoxP3, as well as almost doubled Helios expression. Peripheral Tregs in MS patients have decreased demethylation of FoxP3 gene promoter in comparison with donors. On the contrary, eTregs showed stable up-regulated demethylation without difference between MS patients and donors. MS patients’ and donors’ eTregs have much more suppressive ability than pTregs. Our data showed that eTregs can be applied as immunotherapy for MS patients and other autoimmune diseases if further investigated.
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Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets

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A Quantitative Analysis of Complexity of Human Pathogen-Specific CD4 T Cell Responses in Healthy M . tuberculosis Infected South Africans

A Quantitative Analysis of Complexity of Human Pathogen-Specific CD4 T Cell Responses in Healthy  M .  tuberculosis  Infected South Africans | Immune-Monitoring | Scoop.it
Author Summary Human pathogen-specific immune responses are tremendously complex and the techniques to study them ever expanding. There is an urgent need for a quantitative analysis and better understanding of pathogen-specific immune responses. Mycobacterium tuberculosis (Mtb) is one of the leading causes of mortality due to an infectious agent worldwide. Here, we were able to quantify the Mtb-specific response in healthy individuals with Mtb infection from South Africa. The response is highly diverse and 66 epitopes are required to capture 80% of the total reactivity. Our study also show that the majority of the identified epitopes are restricted by multiple HLA alleles. Thus, technical advances are required to capture and characterize the complete pathogen-specific response. This study demonstrates further that the approach combining identified epitopes into “megapools” allows capturing a large fraction of the total reactivity. This suggests that this technique is generally applicable to the characterization of immunity to other complex pathogens. Together, our data provide for the first time a quantitative analysis of the complex pathogen-specific T cell response and provide a new understanding of human infections in a natural infection setting.
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Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection

Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection | Immune-Monitoring | Scoop.it
Author Summary After being infected with HIV, the pace of disease progression is highly variable between individuals. Some stay well with functioning immune systems for many years, whilst others progress to AIDS quickly.
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Expression of human T cell immunoglobulin domain and mucin-3 (TIM-3) and TIM-3 ligands in peripheral blood from patients with systemic lupus erythematosus - Online First - Springer

Expression of human T cell immunoglobulin domain and mucin-3 (TIM-3) and TIM-3 ligands in peripheral blood from patients with systemic lupus erythematosus - Online First - Springer | Immune-Monitoring | Scoop.it
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Partial recovery of senescence and differentiation disturbances in CD8+ T cell effector-memory cells in HIV-1 infection after initiation of ART - Eberhard - Clinical & Experimental Immunology - Wil...

Partial recovery of senescence and differentiation disturbances in CD8+ T cell effector-memory cells in HIV-1 infection after initiation of ART - Eberhard - Clinical & Experimental Immunology - Wil... | Immune-Monitoring | Scoop.it
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Higher frequency of peripheral blood follicular regulatory T cells in patients with new onset ankylosing spondylitis - Shan - 2015 - Clinical and Experimental Pharmacology and Physiology - Wiley On...

Higher frequency of peripheral blood follicular regulatory T cells in patients with new onset ankylosing spondylitis - Shan - 2015 - Clinical and Experimental Pharmacology and Physiology - Wiley On... | Immune-Monitoring | Scoop.it
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Interferon-|[beta]| therapy specifically reduces pathogenic memory B cells in multiple sclerosis patients by inducing a FAS-mediated apoptosis : Immunology and Cell Biology

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Association of γδ T Cell Compartment Size to Disease Activity and Response to Therapy in SLE

Association of γδ T Cell Compartment Size to Disease Activity and Response to Therapy in SLE | Immune-Monitoring | Scoop.it

Although γδT cells are widely recognized as pivotal elements in immune-mediated diseases, their role in the pathogenesis of SLE and therapeutic outcome remains under explored. The current study aims to characterize the γδT cell compartment in SLE and correlate its status to disease severity and response to therapy.   Conclusions: A strong association exists between γδ T cell compartments and SLE pathogenesis, disease severity and response to therapy.

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Novel flow cytometry identified T-cell signatures of vedolizumab responders

Novel flow cytometry identified T-cell signatures of vedolizumab responders | Immune-Monitoring | Scoop.it
SAN DIEGO – A novel prescreening flow cytometry panel distinguished patients with inflammatory bowel disease who responded to vedolizumab from nonre... More »
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Are the reference values of B cell subpopulations used in adults for classification of common variable immunodeficiencies appropriate for children?

Are the reference values of B cell subpopulations used in adults for classification of common variable immunodeficiencies appropriate for children? | Immune-Monitoring | Scoop.it
Our data stress the importance of age-specific reference values for the correct interpretation of B cell subsets in children as a diagnostic tool in immunodeficiencies.
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CD21–/low B cells in human blood are memory cells

CD21–/low B cells in human blood are memory cells | Immune-Monitoring | Scoop.it
The complement receptor 2 (CR2, CD21) is part of a complex (CD21/CD19/CD81) acting as a co-receptor to the B cell receptor (BCR). Simultaneous triggering of the BCR and CD21 lowers the threshold for B cell activation.
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Expanded CD4+ Effector/Memory T Cell Subset in APECED Produces Predominantly Interferon Gamma

Expanded CD4+ Effector/Memory T Cell Subset in APECED Produces Predominantly Interferon Gamma | Immune-Monitoring | Scoop.it
Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is a rare human autoimmune disorder caused by mutations in the AIRE (autoimmune regulator) gene. Loss of AIRE disrupts thymic negative selection and gives rise to impaired cytotoxic and regulatory T cell populations. To date, CD4+ T helper (Th) cells remain little studied. This study aims to elucidate their role in APECED pathogenesis.These data reveal abnormalities in the Th population and suggest that they may in part be traced to premature activation already in the thymus.
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Polysaccharide-specific Memory B-cells Predict Protection Against Experimental Human Pneumococcal Carriage

Our data indicate that naturally acquired polysaccharide-specific memory B-cells, but not levels of circulating IgG at time of pneumococcal exposure, are associated with protection against carriage acquisition.
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Tumor antigen–specific T cells for immune monitoring of dendritic cell–treated glioblastoma patients - Cytotherapy

These data indicate that GBM tumor peptide-dextramer staining of CTL in combination with intracellular IFN-γ staining may be a useful tool to acquire information on whether a specific tumor antigen has the potential to induce an immune response in vivo.
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New easy-to-use TB test achieves accuracy comparable to IGRAs in phase III trials

A new skin test for tuberculosis infection has proven safe, easy to administer and accurate in two Phase III clinical trials.
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Increased Frequency of BK Virus-Specific Polyfunctional CD8+... : Transplantation

Background: BK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control.

Methods: Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation.

Results: BK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a.

Conclusions: Noninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia.
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Tuberculosis Therapy Modifies the Cytokine Profile, Maturation State, and Expression of Inhibitory Molecules on Mycobacterium tuberculosis -Specific CD4 + T-Cells

Tuberculosis Therapy Modifies the Cytokine Profile, Maturation State, and Expression of Inhibitory Molecules on  Mycobacterium tuberculosis -Specific CD4 +  T-Cells | Immune-Monitoring | Scoop.it
Background Little is known about the expression of inhibitory molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed-death-1 (PD-1) on Mycobacterium tuberculosis (Mtb)-specific CD4 T-cells and how their expression is impacted by TB treatment. Methods Cryopreserved PBMCs from HIV-TB co-infected and TB mono-infected patients with untreated and treated tuberculosis (TB) disease were stimulated for six hours with PPD and stained. Using polychromatic flow cytometry, we characterized the differentiation state, cytokine profile, and inhibitory molecule expression on PPD-specific CD4 T-cells. Results In our HIV-TB co-infected cohort, TB treatment increased the proportion of PPD-specific CD4 T-cells co-producing IFN-γ + IL-2 + TNF-α + and IFN-γ + IL-2 + (p = 0.0004 and p = 0.0002, respectively) while decreasing the proportion of PPD-specific CD4 T-cells co-producing IFN-γ + MIP1-β + TNF-α + and IFN-γ + MIP1-β + . The proportion of PPD-specific CD4 T-cells expressing an effector memory phenotype decreased (63.6% vs 51.6%, p = 0.0015) while the proportion expressing a central memory phenotype increased (7.8% vs. 21.7%, p = 0.001) following TB treatment. TB treatment reduced the proportion of PPD-specific CD4 T-cells expressing CTLA-4 (72.4% vs. 44.3%, p = 0.0005) and PD-1 (34.5% vs. 29.2%, p = 0.03). Similar trends were noted in our TB mono-infected cohort. Conclusion TB treatment alters the functional profile of Mtb-specific CD4 T-cells reflecting shifts towards a less differentiated maturational profile and decreases PD-1 and CTLA-4 expression. These could serve as markers of reduced mycobacterial burden. Further study is warranted.
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Decreased Frequencies of Circulating Follicular Helper T Cell Counterparts and Plasmablasts in Ankylosing Spondylitis Patients Naïve for TNF Blockers

Decreased Frequencies of Circulating Follicular Helper T Cell Counterparts and Plasmablasts in Ankylosing Spondylitis Patients Naïve for TNF Blockers | Immune-Monitoring | Scoop.it
Follicular helper T cells (Tfh), localized in lymphoid organs, promote B cell differentiation and function. Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of Tfh. Three subpopulations of circulating CD4+CXCR5+ cells have been described: CXCR3+CCR6- (Tfh-Th1), CXCR3-CCR6+ (Tfh-Th17), and CXCR3-CCR6- (Tfh-Th2). Only Tfh-Th17 and Tfh-Th2 function as B cell helpers. Our objective was to study the frequencies of circulating Tfh (cTfh), cTfh subsets and plasmablasts (CD19+CD20-CD27+CD38 high cells), and the function of cTfh cells, in patients with Ankylosing Spondylitis (AS). To this end, peripheral blood was drawn from healthy controls (HC) (n = 50), AS patients naïve for TNF blockers (AS/nb) (n = 25) and AS patients treated with TNF blockers (AS/b) (n = 25). The frequencies of cTfh and plasmablasts were determined by flow cytometry. Cocultures of magnetically sorted CD4+CXCR5+ T cells with autologous CD19+CD27- naïve B cells were established from 3 AS/nb patients and 3 HC, and concentrations of IgG, A and M were measured in supernatants. We obseved that AS/nb but not AS/b patients, demonstrated decreased frequencies of circulating CD4+CXCR5+ICOS+PD-1+ cells and plasmablasts, together with a decreased (Tfh-Th17+Tfh-Th2)/Tfh-Th1 ratio. The amounts of IgG and IgA produced in cocultures of CD4+CXCR5+ T cells with CD19+CD27- B cells of AS/nb patients were significantly lower than observed in cocultures established from HC. In summary, AS/nb but not AS/b patients, demonstrate a decreased frequency of cTfh and plasmablasts, and an underrepresentation of cTfh subsets bearing a B helper phenotype. In addition, peripheral blood CD4+CXCR5+ T cells of AS/nb patients showed a decreased capacity to help B cells ex vivo.
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Higher Frequency of Peripheral Blood Interleukin 21 Positive Follicular Helper T Cells in Patients with Ankylosing Spondylitis

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Cellular & Molecular Immunology - Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions

Cellular & Molecular Immunology - Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions | Immune-Monitoring | Scoop.it
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Th17/Treg Imbalance Induced by Dietary Salt Variation Indicates Inflammation of Target Organs in Humans

Th17/Treg Imbalance Induced by Dietary Salt Variation Indicates Inflammation of Target Organs in Humans | Immune-Monitoring | Scoop.it
The functions of T helper 17 (Th17) and regulatory T (Treg) cells are tightly orchestrated through independent differentiation pathways that are involved in the secretion of pro- and anti-inflammatory cytokines induced by high-salt dietary.
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JCI Insight - T cell Bim levels reflect responses to anti–PD-1 cancer therapy

JCI Insight - T cell Bim levels reflect responses to anti–PD-1 cancer therapy | Immune-Monitoring | Scoop.it
RT @PrashantBavi: In melanoma, bim1 expression may predict response to anti pd-l1 Rx https://t.co/PXqAcFPywg #PD-L1 #cancer https://t.co/X…

Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+ T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility.

Via Krishan Maggon
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CD21−/low B cells: A Snapshot of a Unique B Cell Subset in Health and Disease - Thorarinsdottir - 2015 - Scandinavian Journal of Immunology - Wiley Online Library

CD21−/low B cells: A Snapshot of a Unique B Cell Subset in Health and Disease - Thorarinsdottir - 2015 - Scandinavian Journal of Immunology - Wiley Online Library | Immune-Monitoring | Scoop.it
The successful treatment of patients with autoimmune diseases with either B cell depletion therapy (rituximab) or inhibition of B cell survival (belimumab), suggested that not only the autoantibodies but also other B cell features are important. This has caused a surge of interest in B cells and their biology resulting in the identification of various subsets e.g. regulatory B cells, several memory B cell subsets etc. Also, in other conditions such as chronic viral infections and primary immunodeficiency, several B cell subsets with unique characteristics have been identified. In this review, we will discuss one of these subsets, a subset that is expanded in conditions characterized by chronic immune stimulation. This B cell subset lacks, or expresses low, surface levels of the complement receptor 2 (CD21) and has therefore been termed CD21−/low B cells.
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