'Membrane-damaged cells caused by either mechanical trauma or through normal biological processes can produce artifacts in immunophenotyping analysis by flow cytometry. Dead cells can nonspecifically bind monoclonal antibody conjugates, potentially leading to erroneous conclusions, particularly when cell frequencies are low. To date, DNA intercalating dyes (Ethidium monoazaide (EMA), Propidium Iodide, ... More
Levels of circulating endothelial cells are low in idiopathic pulmonary fibrosis and are further reduced by anti-fibrotic treatments.
AuthorsDe Biasi S, Cerri S, Bianchini E, Gibellini L, Persiani E, Montanari G, Luppi F, Carbonelli CM, Zucchi L, Bocchino M, Zamparelli AS, Vancheri C, Sgalla G, Richeldi L, Cossarizza A,
Journal
PubMed ID26552487
'It has been suggested that circulating fibrocytes and endothelial cells actively participate in the intense remodelling of the pulmonary vasculature in patients with idiopathic pulmonary fibrosis (IPF). Indeed, fibrotic areas exist that have fewer blood vessels, whereas adjacent non-fibrotic tissue is highly vascularized. The number of circulating endothelial cells (CEC) ... More
IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures.
AuthorsBlom L, Poulsen LK,
JournalJ Immunol
PubMed ID23028054
'The IL-1 family members IL-1ß, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood donors, and reactivated in the ... More
Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion.
AuthorsRalston KS, Solga MD, Mackey-Lawrence NM, Somlata, Bhattacharya A, Petri WA,
Journal
PubMed ID24717428
'Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrhoeal disease in the developing world. The parasite was named '
Establishment of an aerosol challenge model of tuberculosis in rhesus macaques and an evaluation of endpoints for vaccine testing.
AuthorsSharpe SA, McShane H, Dennis MJ, Basaraba RJ, Gleeson F, Hall G, McIntyre A, Gooch K, Clark S, Beveridge NE, Nuth E, White A, Marriott A, Dowall S, Hill AV, Williams A, Marsh PD,
JournalClin Vaccine Immunol
PubMed ID20534795
'The establishment of an aerosol challenge model in nonhuman primates (NHPs) for the testing of vaccines against Mycobacterium tuberculosis would assist the global effort to optimize novel vaccination strategies. The endpoints used in preclinical challenge studies to identify measures of disease burden need to be accurate and sensitive enough to ... More
Regulatory T Cells Prevent Th2 Immune Responses and Pulmonary Eosinophilia during Respiratory Syncytial Virus Infection in Mice.
AuthorsDurant LR, Makris S, Voorburg CM, Loebbermann J, Johansson C, Openshaw PJ,
Journal
PubMed ID23926350
'During viral infection, inflammation and recovery are tightly controlled by competing proinflammatory and regulatory immune pathways. Respiratory syncytial virus (RSV) is the leading global cause of infantile bronchiolitis, which is associated with recurrent wheeze and asthma diagnosis in later life. Th2-driven disease has been well described under some conditions for ... More
Defective immunoregulation in RSV vaccine-augmented viral lung disease restored by selective chemoattraction of regulatory T cells.
AuthorsLoebbermann J, Durant L, Thornton H, Johansson C, Openshaw PJ,
JournalProc Natl Acad Sci U S A
PubMed ID23382205
'Human trials of formaldehyde-inactivated respiratory syncytial virus (FI-RSV) vaccine in 1966-1967 caused disastrous worsening of disease and death in infants during subsequent natural respiratory syncytial virus (RSV) infection. The reasons behind vaccine-induced augmentation are only partially understood, and fear of augmentation continues to hold back vaccine development. We now show ... More
Blockade of IL-10 signaling during bacillus Calmette-Guérin vaccination enhances and sustains Th1, Th17, and innate lymphoid IFN-? and IL-17 responses and increases protection to Mycobacterium tuberculosis infection.
AuthorsPitt JM, Stavropoulos E, Redford PS, Beebe AM, Bancroft GJ, Young DB, O'Garra A,
JournalJ Immunol
PubMed ID22972927
Vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) remains the only prophylactic vaccine against tuberculosis, caused by Mycobacterium tuberculosis, but gives variable protection against pulmonary disease. The generation of host Th1 responses following BCG vaccination is accepted as the major mechanism of protection against M. tuberculosis infection. Early production of IL-17 ... More
Differential requirement for CD70 and CD80/CD86 in dendritic cell-mediated activation of tumor-tolerized CD8 T cells.
AuthorsBak SP, Barnkob MS, Bai A, Higham EM, Wittrup KD, Chen J,
JournalJ Immunol
PubMed ID22798683
A major obstacle to efficacious T cell-based cancer immunotherapy is the tolerizing-tumor microenvironment that rapidly inactivates tumor-infiltrating lymphocytes. In an autochthonous model of prostate cancer, we have previously shown that intratumoral injection of Ag-loaded dendritic cells (DCs) delays T cell tolerance induction as well as refunctionalizes already tolerized T cells ... More
High-throughput screen using a single-cell tyrosine phosphatase assay reveals biologically active inhibitors of tyrosine phosphatase CD45.
Many cellular signaling events are regulated by tyrosine phosphorylation and mediated by the opposing actions of protein tyrosine kinases and phosphatases. Protein tyrosine phosphatases are emerging as drug targets, but poor cell permeability of inhibitors has limited the development of drugs targeting these enzymes [Tautz L, et al. (2006) Expert ... More
Regulatory T cells control HIV replication in activated T cells through a cAMP-dependent mechanism.
AuthorsMoreno-Fernandez ME, Rueda CM, Rusie LK, Chougnet CA,
JournalBlood
PubMed ID21436067
We hypothesized that regulatory T cells (Tregs) could play a beneficial role during HIV infection by controlling HIV replication in conventional T cells (Tcons). Purified Tregs and Tcons from healthy donors were activated separately. Tcons were infected with the X4 or R5 HIV strains and cultured with or without autologous ... More
A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus.
AuthorsPilsczek FH, Salina D, Poon KK, Fahey C, Yipp BG, Sibley CD, Robbins SM, Green FH, Surette MG, Sugai M, Bowden MG, Hussain M, Zhang K, Kubes P,
JournalJ Immunol
PubMed ID21098229
Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe ... More
Dendritic cells induce regulatory T cell proliferation through antigen-dependent and -independent interactions.
Regulatory T cells (Tregs) are a subset of T cells with suppressive function that protect the host from autoimmunity and prevent excessive immunopathology. Functional Tregs must be present throughout life to provide continuous protection for the host. Despite the intense study of this lineage, the mechanisms by which Tregs are ... More
Activation of tolerogenic dendritic cells in the tumor draining lymph nodes by CD8+ T cells engineered to express CD40 ligand.
AuthorsHigham EM, Wittrup KD, Chen J,
JournalJ Immunol
PubMed ID20200275
Tolerogenic dendritic cells in the tumor microenvironment can inhibit the generation and maintenance of robust antitumor T cell responses. In this study, we investigated the effects of local delivery of CD40L by tumor-reactive CD8(+) T cells on dendritic cell activation and antitumor T cell responses in the TRAMP model. To ... More
Tissue-specific differences in PD-1 and PD-L1 expression during chronic viral infection: implications for CD8 T-cell exhaustion.
AuthorsBlackburn SD, Crawford A, Shin H, Polley A, Freeman GJ, Wherry EJ,
JournalJ Virol
PubMed ID19955307
The PD-1/PD-L pathway plays a major role in regulating T-cell exhaustion during chronic viral infections in animal models, as well as in humans, and blockade of this pathway can revive exhausted CD8(+) T cells. We examined the expression of PD-1 and its ligands, PD-L1 and PD-L2, in multiple tissues during ... More
Depletion of passenger leukocytes from corneal grafts: an effective means of promoting transplant survival?
AuthorsZhang X, Shen L, Jin Y, Saban DR, Chauhan SK, Dana R,
JournalInvest Ophthalmol Vis Sci
PubMed ID19136708
To develop and compare effective strategies for depleting graft-derived passenger leukocytes that include antigen-presenting cells from corneal buttons and to assess the effectiveness of this strategy in promoting graft survival using a high-risk (HR) model of corneal transplantation. Corneal buttons harvested from C57BL/6 mice were used in three ex vivo ... More
Utility of magnetic resonance imaging and nuclear magnetic resonance-based metabolomics for quantification of inflammatory lung injury.
AuthorsSerkova NJ, Van Rheen Z, Tobias M, Pitzer JE, Wilkinson JE, Stringer KA,
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID18441091
Magnetic resonance imaging (MRI) and metabolic nuclear magnetic resonance (NMR) spectroscopy are clinically available but have had little application in the quantification of experimental lung injury. There is a growing and unfulfilled need for predictive animal models that can improve our understanding of disease pathogenesis and therapeutic intervention. Integration of ... More
Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components.
AuthorsAlici E, Sutlu T, Björkstrand B, Gilljam M, Stellan B, Nahi H, Quezada HC, Gahrton G, Ljunggren HG, Dilber MS,
JournalBlood
PubMed ID18192509
Multiple myeloma (MM) is an incurable plasma cell malignancy with poor outcome. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy, and immunotherapy. Cell-based immunotherapy after hematopoietic stem-cell transplantation has been attempted, but with limited efficacy. Natural killer (NK) cells are interesting candidates for new means ... More
Aggregate formation inhibits proteasomal degradation of polyglutamine proteins.
Insoluble protein aggregates are consistently found in neurodegenerative disorders caused by expanded polyglutamine [poly(Q)] repeats. The aggregates contain various components of the ubiquitin/proteasome system, suggesting an attempt of the cell to clear the aberrant substrate. To investigate the effect of expanded poly(Q) repeats on ubiquitin/proteasome-dependent proteolysis, we targeted these proteins ... More
SYTO probes in the cytometry of tumor cell death.
AuthorsWlodkowic D, Skommer J, Darzynkiewicz Z,
JournalCytometry A
PubMed ID18260152
Apoptosis is a complex and finely controlled cell death process of great relevance in tissue homeostasis and pathogenesis. The majority of classical apoptotic features can be examined by flow as well as image cytometry. Therefore, cytometry has been used as a technology of choice in studies of tumor cell demise. ... More
Epididymosomes transfer epididymal sperm binding protein 1 (ELSPBP1) to dead spermatozoa during epididymal transit in bovine.
AuthorsD'Amours O, Frenette G, Bordeleau LJ, Allard N, Leclerc P, Blondin P, Sullivan R
JournalBiol Reprod
PubMed ID22875906
Previously, we showed that epididymal sperm binding protein 1 (ELSPBP1) characterizes spermatozoa already dead before ejaculation in bovine. In this study, we investigated the presence of ELSPBP1 in bull genital tract as well as its acquisition by spermatozoa during epididymal transit. As assessed by real-time RT-PCR, ELSPBP1 was highly expressed ... More