Search results for "Immunological"
showing 10 items of 115 documents
In vitro model for the activation of CD4 and CD8 T cell receptors.
2008
Previously, most models that sought to explain the misregulation of immune cell function assumed molecular similarities between the disease-causing pathogens and the host's proteins. In recent time several different models have been proposed and in this study, these concepts are compared to a new hypothesis proposing another explanation for this immune dysregulation: the possibility that the mislocalization of proteins may be responsible for autoimmune activity. Based on this hypothesis, proteins are recognized as self or non-self depending on where they appear in sufficiently high concentrations. To examine this new idea, the intracellular human proteins beta-actin, GAPDH, and hemoglobin a…
Stochastic Episodes of Latent Cytomegalovirus Transcription Drive CD8 T-Cell “Memory Inflation” and Avoid Immune Evasion
2021
Acute infection with murine cytomegalovirus (mCMV) is controlled by CD8+ T cells and develops into a state of latent infection, referred to as latency, which is defined by lifelong maintenance of viral genomes but absence of infectious virus in latently infected cell types. Latency is associated with an increase in numbers of viral epitope-specific CD8+ T cells over time, a phenomenon known as “memory inflation” (MI). The “inflationary” subset of CD8+ T cells has been phenotyped as KLRG1+CD62L- effector-memory T cells (iTEM). It is agreed upon that proliferation of iTEM requires repeated episodes of antigen presentation, which implies that antigen-encoding viral genes must be transcribed du…
Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells
2001
Abstract Background: Dendritic cells (DCs) are able to induce human allergic T H 1 responses as well as T H 2 responses. Objective: In this study, we examined the effect of antiinflammatory agents such as IL-10 and hydrocortisone (HC) on the accessory function of DCs and the resulting T-cell response, especially that of T H 2 cells. Methods: Naive and memory CD4 + T cells from atopic donors were stimulated with autologous allergen-pulsed DCs generated from CD14 + monocytes by culture with GM-CSF/IL-4 and fully matured with IL-1β, TNF-α, and PGE 2 in the presence or absence of IL-10 or HC. Results: IL-10–treated DCs and, to a lesser extent, HC-treated DCs showed a decreased expression of MHC…
Atypical Human Effector/Memory CD4(+) T Cells With a Naive-Like Phenotype
2018
The induction of adaptive immunological memory, mediated by T and B cells, plays an important role in protective immunity to pathogens induced by previous infections or vaccination. Naive CD4+ T cells that have been primed by antigen develop into memory or effector cells, which may be distinguished by their capability to exert a long-term and rapid response upon re-challenge by antigen, to produce distinct cytokines and surface marker expression phenotypes such as CD45RA/RO, CD27, CD62L, and CCR7. Moreover, a distinct lineage of memory T cells populates tissues (tissue-resident memory T cells or TRM cells) which orchestratea the response to pathogens re encountered at tissue sites. Recent e…
Efficacy and safety of first-line checkpoint inhibitors-based treatments for non-oncogene-addicted non-small-cell lung cancer: a systematic review an…
2021
Background: Frontline immune checkpoint inhibitors (ICI)-based regimens in non-oncogene-addicted non-small-cell lung cancer (NSCLC) have been deeply investigated. To rank the available therapeutic options, we carried out a systematic review and Bayesian meta-analysis. Methods: A comprehensive search for randomized controlled trials (RCTs) of ICI regimens, and a pairwise and a network meta-analysis (NMA) with an all-comers and a stratified strategy were conducted. Endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs). Results: Nineteen RCTs involving 17 treatment regimens were included. For the all-co…
Preclinical and Clinical Characterization of Fibroblast-derived Neuregulin-1 on Trastuzumab and Pertuzumab Activity in HER2-positive Breast Cancer.
2021
[Purpose]: To characterize expression of neuregulin-1 (NRG1), an HER3 ligand, in HER2-positive breast cancer and its relation with the efficacy of trastuzumab with or without pertuzumab.
Clinico-Immunological Status and Neurocognitive Function of Perinatally Acquired HIV-Positive Children on cART: A Cross-Sectional Correlational Study…
2020
Despite the undisputed benefits of combination antiretroviral therapy (cART), perinatally acquired human immunodeficiency virus (PHIV) children on treatment often present with a spectrum of neurological deficits known as HIV-associated neurocognitive impairment. Even higher CD4 cell count does not seem to prevent the development of neurocognitive impairment in children with PHIV. While CD4 cell count has shown to have the greatest prognostic value, its association with neurocognitive abilities remains to be clarified. This study aimed at determining the correlation between plasma CD4+ lymphocyte and neurocognitive function in children with PHIV on cART. In total, 152 purposively recruited h…
Th9 cells, new players in adaptive immunity.
2014
Upon antigen-specific stimulation, naive CD4⁺ T cells have the potential to differentiate into various T helper (Th) cell subsets. Earlier models of Th cell differentiation focused on IFN-γ-producing Th1 cells and IL-4-secreting Th2 cells. The discovery of additional CD4⁺ Th cell subsets has extended our understanding of Th cell differentiation beyond this dichotomy. Among these is the recently described Th9 cell subset, which preferentially produces interleukin (IL)-9. Here, we review the latest developments in Th9 cell development and differentiation, focusing on contributing environmental signals, and discuss potential physiological and pathophysiological functions of these cells. We des…
NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling
2018
NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIKΔT) mice. Despite showing normal development of lymphoid organs, NIKΔT mice were resistant to induction of CNS autoimmunity. T cells from NIKΔT mice were deficient in late priming, failed to up-regulate T-bet and to transmigrate into the CNS. Proteomic analysis of activated NIK-/- T cells showed de-regulated expression of proteins involved in the formation of the immunological synapse: in particular, proteins involved in cytoskeleton dy…
Organization and evolution of synthetic idiotypic networks
2012
We introduce a class of weighted graphs whose properties are meant to mimic the topological features of idiotypic networks, namely the interaction networks involving the B-core of the immune system. Each node is endowed with a bit-string representing the idiotypic specificity of the corresponding B cell and a proper distance between any couple of bit-strings provides the coupling strength between the two nodes. We show that a biased distribution of the entries in bit-strings can yield fringes in the (weighted) degree distribution, small-worlds features, and scaling laws, in agreement with experimental findings. We also investigate the role of ageing, thought of as a progressive increase in …