Heavy functions for light chains.
Explore the source record for details and available documents.
Humans↗
SEARCH · Search PubMed
Results for “Immunologic Memory”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Murine models of drug hypersensitivity.
PURPOSE OF REVIEW: Drug hypersensitivity reactions are relatively rare but may result in severe morbidity and fatalities. Due to the idiosyncratic nature and multifactorial etiology of these reactions, development of a single animal model to study the immunosensitizing mechanisms of all drugs is impossible. This hampers the development of predictive screening models that are urgently needed to assess the immunostimulating capacity of newly developed drugs. The present review will focus on recent findings on mechanisms of drug hypersensitivity reactions obtained with murine models, and on the use of these models as potential screening tools to assess the immunostimulating capacity of drugs. RECENT FINDINGS: Mechanisms of drug-induced sensitization versus tolerance appear dependent on generally accepted immunological paradigms. For instance, co-stimulatory signaling by antigen-presenting cells is decisive in drug-induced immunosensitization and both T cells and antigen-presenting cells are important for the induction of tolerance to orally administered drugs. From recent studies it has been hypothesized that expression of stress-associated transcription factors and the expression of costimulatory molecules or cytokine production within hours or days after the initial exposure may be representative of drug-induced hypersensitivity reactions and may thus be used as predictive parameters to screen for immunosensitizing drugs. SUMMARY: The development of animal models to study mechanisms of drug hypersensitivity reactions is still in its infancy. Much effort has been made, however, to search for early indicators of immunostimulation in murine animal models that may eventually appear useful in a tiered strategy to assess drug-induced sensitization.
Animals↗
A comprehensive meta-analysis of tissue resident memory T cells and their roles in shaping immune microenvironment and patient prognosis in non-small cell lung cancer.
Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification.
Humans↗
[Xenogeneic corneal grafting. I. Active and passive sensitizing of the rat against guinea pig cornea].
Explore the source record for details and available documents.
Animals↗
Radiation-induced alterations in murine lymphocyte homing patterns. II. Recovery and function of memory cells in LBN rats.
Explore the source record for details and available documents.
Animals↗
Reshaping the past: Strategies for modulating T-cell memory immune responses.
Memory T cells are generated following an initial encounter with antigen, persist over the lifetime of an individual, and mediate rapid and robust functional responses upon antigenic recall. While immune memory is generally associated with protective immune response to pathogens, memory T cells can be generated to diverse types of antigens including autoantigens and alloantigens through homologous or crossreactive priming and comprise the majority of circulating T cells during adulthood. Memory T cells can therefore play critical roles in propagating and perpetuating autoimmune disease and in mediating allograft rejection, although the precise pathways for regulation of memory immune responses remain largely undefined. Moreover, evaluating and designing strategies to modulate memory T-cell responses are challenging given the remarkable heterogeneity of memory T cells, with different subsets predominating in lymphoid versus non-lymphoid tissue sites. In this review, we discuss what is presently known regarding the effect of current immunomodulation strategies on the memory T-cell compartment and potential strategies for controlling immunological recall.
Animals↗
Tumor escape from immune elimination: simplified precursor bound cytotoxicity models.
In this paper we present a series of models on cytotoxic T-cell activation derived, by successive simplifications, from the model for Tumor Escape from Immune Elimination of Grossman & Berke (1980). In their model Grossman & Berke (1980) investigate the "sneaking through" phenomenon, by which they mean that small tumors grow progressively, medium-sized tumors are rejected and large ones break through again. We define precursor bound cytotoxicity models as systems incapable of infinite proliferation. We show that sneaking through can occur in a broad class of very simple precursor bound cytotoxicity models due to the depletion of the precursor cells. The simplest process by which precursors can be depleted is long-lasting antigenic stimulation. We conclude that in precursor bound cytotoxicity models sneaking through does not need the rather intricate combination of counteracting feedback loops, memory and blocking described by Grossman & Berke (1980).
Antigens, Neoplasm↗
Immunosurveillance modelled in vitro: naive and memory T cells spontaneously migrate across unstimulated microvascular endothelium.
As a model for T cell immigration into non-lymphoid tissue we set up an in vitro assay that would allow us to investigate the phenotype of T lymphocytes from peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) or peripheral blood (PBL) of mice, which were able to spontaneously migrate across unstimulated microvascular endothelium. The transendothelial migrating T cell population was enriched for T lymphocytes expressing a "recently activated/memory' phenotype: LFA-1/CD44/ICAM-1high, but also contained CD45RBhigh and LFA-1low T cells, which in the case of MLN T cells were phenotyped as CD4+ and thus characterized as naive T cells. Transmigrated T cells could be further distinguished from their original populations and from each other by their distinct but heterogeneous expression patterns for L-selectin, alpha 4 beta 7-integrin and PECAM-1. This observation suggests the presence of phenotypically different migratory T cells among MLN, PLN and PBL. Additional studies provided evidence that the capacity to migrate across unstimulated microvascular endothelium was a characteristic of a T cell population that could phenotypically be differentiated from activated T cells. The endothelial cells were found to play an active role in selecting the traversing T cell population, as they controlled the number and phenotype of spontaneously transmigrating T cells. Our studies suggest that the capacity to transmigrate across unstimulated microvascular endothelium and hence to immigrate into non-lymphoid tissue is owned by a phenotypically heterogeneous T cell population, which is enriched for memory T cells but not devoid of naive T cells.
Animals↗
IL-15-independent proliferative renewal of memory CD8+ T cells in latent gammaherpesvirus infection.
IL-15 is known to be critical in the homeostasis of Ag-specific memory CD8(+) T cells following acute viral infection. However, little is known about the homeostatic requirements of memory CD8(+) T cells during a latent viral infection. We have used the murine gammaherpesvirus-68 (MHV-68) model system to investigate whether IL-15 is necessary for the maintenance of memory CD8(+) T cells during a latent viral infection. IL-15 is not essential either for the initial control of MHV-68 infection or for the maintenance of MHV-68-specific memory CD8(+) T cells. Even at 140 days postinfection, the proportion of CD8(+) T cells recognizing the MHV-68 epitopes were the same as in control mice. The maintenance of these memory CD8(+) T cells was attributable to their ability to turn over in vivo, probably in response to the presence of low levels of Ag. IL-15(-/-) mice had a significantly higher turnover rate within the virus-specific memory CD8(+) T cell population, which was the result of increased levels of viral gene expression rather than an increase in viral load. These cells did not accumulate in the spleens of the IL-15(-/-) mice due to an increased sensitivity to apoptosis as a result of decreased Bcl-2 levels. Intriguingly, memory CD8(+) T cells from latently infected mice failed to undergo homeostatic proliferation in a naive secondary host. These data highlight fundamental differences between memory CD8(+) T cells engaged in active immune surveillance of latent viral infections vs memory CD8(+) T cells found after acute viral infections.
Adoptive Transfer↗
Thanks for the memory!
Explore the source record for details and available documents.
Allergy and Immunology↗
Peripheral blood T cell proliferative response to chlamydial organisms in gonococcal and non-gonococcal urethritis and presumed pelvic inflammatory disease.
OBJECTIVE: To study peripheral blood mononuclear cell (PBMC) proliferative response to Chlamydia trachomatis elementary bodies in (a) controls, (b) various stages of gonococcal (c) and non-gonococcal urethritis, and (d) women with a clinical diagnosis of pelvic inflammatory disease (PID). METHODS: We categorised 102 men presenting to a GUM clinic with urethritis by organisms (C trachomatis (CT) or Neisseria gonorrhoeae (NG) (both by culture), and whether it was their first (urethritis naive) or subsequent (urethritis experienced) attack. 23 women presenting to the clinic with a clinical diagnosis of PID were also investigated. We measured PBMC proliferative responses to C trachomatis (DK20--an oculogenital strain, serovar E), lysate of McCoy cells (used to propagate chlamydiae), and the recall antigen PPD. Controls were 37 men and women without present or past history of urethritis or chlamydial infection. Results were expressed as the ratio of the stimulation index (SI) obtained with DK20 compared with McCoy cells (DK index), and the ratio of the SI obtained with DK20 compared with PPD (PPD index). RESULTS: The median SI to DK20 in the urethritis was 12.7 which was significantly higher than the controls (7.6, p < 0.003). The median SI to the recall antigen PPD was similar in the urethritis patients (17.4) and the controls (22.4). All urethritis patient subgroups had a significantly higher DK index and PPD index than the controls. There was no difference in the PPD and DK index between urethritis naive and urethritis experienced patients and between the culture positive and culture negative urethritis subgroups. In PID patients only the PPD index was significantly higher than the controls. CONCLUSION: Men presenting with urethritis and women presenting with PID both have significantly greater peripheral blood mononuclear cell proliferative responses to the DK20 strain of C trachomatis than controls. A similar T cell proliferative response pattern in urethritis naive patients with either gonococcal or non-gonococcal urethritis could be because low sensitivity of CT culture failed to diagnose some cases of C trachomatis. However, it may also signify earlier exposure of the patients to chlamydial antigens (for example, C pneumoniae), cross reacting antigens such as heat shock proteins from other microbial species, or a "bystander" activation of chlamydia specific memory T cells trafficking through mucosal lymphoid tissue during urethritis. These results suggest evidence of T cell mediated response to C trachomatis cannot be used as a diagnostic tool.
Adult↗
New bioassay for screening immunotoxic agents.
A new bioassay for evaluation of compounds potentially toxic for the immune system is described. It is suitable for the measurement of enhancement of primary antibody response and of enhancement and inhibition of memory development in vivo. It utilizes immunoenzymatic techniques which can readily be automated and thus allow the screening of many compounds at relatively low cost. It can provide answers regarding the safety or danger of each compound tested within 30-45 days.
Animals↗
RISH V. Application to monoclonal antibody production.
RISH considers that cell surface components involved in like cell identification are not involved in the structure of the plasma membrane per se and are attached to a part of their mRNA. The mRNA then acts as a template for the synthesis of DNA. Thus the component at the cell surface is attached to an RNA/DNA receptor. If there is a conformational change in the component (antigen) this will cause a distortion in its RNA/DNA receptor. This distortion is then detected by a tissue specific T lymphocyte which removes all or part of the RNA/DNA receptor from the aberrant cell and the lymphocyte then undergoes replication. During this process receptor RNA/DNA is incorporated into the daughter lymphocyte which becomes a B lymphocyte/plasma cell producing immunoglobulin. The initial tissue specific T lymphocyte becomes a dual functional helper/suppressor cell. The plasma cell after the initial immune response becomes a circulating memory B cell displaying IgM or IgD. If this cell complexes an antigen with its surface IgM or IgD a humoral immune response will be developed as previously described, but in this case the antibodies produced will be anti-idiotypic antibodies. The anti-idiotypic antibodies will regulate the production of the antibody directed against the antigen per se. The anti-idiotypic antibodies will in turn be regulated by a second anti-idiotypic antibody. In RISH five such anti-idiotypic systems may be involved in regulating the immune response to the initial non-immunoglobulin antigen. Based on the RISH anti-idiotypic mechanism a system is briefly described whereby human memory B cells, to a particular antigen, may be isolated. These B cells may then be activated to secrete immunoglobulin with autologous isolated anti-idiotypic antibodies. These activated cells may then be infected with E.B. virus to establish an immortal cell line of B cells secreting the immunoglobulin of interest.
Animals↗
Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues.
Antigen-driven T cell education and subsequent pathogen elimination present particular challenges for the immune system. Pathogens generally enter the body at peripheral sites such as the skin, gastrointestinal tract or lung, areas from which naïve T cells are largely excluded. Instead, naïve T cells constantly recirculate through secondary lymphoid organs, such as lymph nodes and Peyer's patches, in search for antigen brought to these locations by means of afferent lymphatic channels. Here, antigen-loaded dendritic cells present antigen-peptide-MHC complexes to clonotypic T cells and provide appropriate co-stimulatory signals for immune response initiation. As a result, short-lived effector T cells and long-lived memory T cells are generated that reach the peripheral tissue for participation in immune responses and immune surveillance. Effector and memory T cell relocation is non-random, due to tissue-specific "address codes" that allow proper tissue homing. This process involves adhesion molecules, including selectins, integrins, and corresponding vascular ligands as well as the large family of chemokines and their receptors. Here, we discuss the changes in chemokine receptor expression that occur during T cell activation and differentiation, and the ways in which these changes impact on the migration potential of naïve, effector, and memory T cells. We summarize our current understanding of T cell homing to the T zone and B cell follicles within secondary lymphoid tissues and highlight the two chemokine receptors CCR7 and CXCR5 that recognize chemokines constitutively present either in the T zone (CCR7 ligands CCL19/ELC and CCL21/SLC) or follicular compartment (CXCR5 ligand CXCL13/BCA-1). CCR7 is characteristic for naive and central memory T (T(CM)) cells whereas CXCR5 distinguishes follicular B helper T (T(FH)) cells. In addition, we further subdivide long-lived memory T cells into CCR7-negative effector memory T (T(EM)) cells and peripheral immune surveillance T (T(PS)) cells. The latter term designates the extraordinarily large subset of memory T cells with primary residence in normal (healthy) peripheral tissues. Our current understanding of T(PS) cell migration and function is highly fragmentary, but these cells are thought to provide immediate protection locally at the site of pathogen entry. Here, we propose that the tissue distribution of T(PS) cells is determined by a distinct set of chemokines and corresponding receptors that differs from those operating in secondary lymphoid tissues and inflammatory sites.
Animals↗
Detection of antigen-specific B cells in patients with pemphigus vulgaris by enzyme-linked immunospot assay: requirement of T cell collaboration for autoantibody production.
Patients with pemphigus vulgaris have circulating IgG autoantibodies against desmoglein 3, which inhibit cell-cell adhesion of keratinocytes and cause blister formation in the skin and mucous membrane. To examine cellular mechanisms underlying the autoantibody production in pemphigus vulgaris patients, we have successfully developed an enzyme-linked immunospot assay which was able to detect desmoglein 3-specific autoimmune B cells quantitatively. Circulating B cells producing anti-desmoglein 3 antibodies were detected exclusively in three patients with severe disease (1.3-2.3/105 peripheral blood mononuclear cells), but not in 10 patients with mild disease or in remission or in seven healthy individuals. When this enzyme-linked immunospot assay was combined with in vitro stimulation of peripheral blood mononuclear cells with pokeweed mitogen and recombinant-desmoglein 3, we could detect circulating desmoglein 3-specific memory B cells in nine of 14 patients (6.3-84. 0/105 peripheral blood mononuclear cells), but in none of 10 healthy individuals. We further analyzed the role of CD4 + T cells in promoting anti-desmoglein 3 antibody production. The in vitro anti-desmoglein 3 antibody production was abolished when CD4 + cells were depleted or when anti-HLA-DR or anti-HLA-DQ monoclonal antibody was added to the cultures. Our results demonstrated the quantitative detection of circulating "activated" and "memory" desmoglein 3-specific B cells and suggested the important part of HLA class II-restricted CD4 + T cells in the autoantibody production in pemphigus vulgaris. In addition, the enzyme-linked immunospot assay in combination with in vitro stimulation of B cells could be broadly applied to study mechanisms for autoantibody production in various autoimmune diseases.
Adult↗
Identification of naturally processed and HLA-presented Epstein-Barr virus peptides recognized by CD4(+) or CD8(+) T lymphocytes from human blood.
The broad clinical implementation of cancer vaccines targeting the induction of specific T cell-mediated immunity is hampered because T cell defined tumor-associated peptides are currently available for only a restricted range of tumor types. Current epitope identification strategies require a priori the generation of T "indicator" cell lines that specifically recognize the tumor antigenic epitope in in vitro assay systems. An alternative to this strategy is the use of "memory" T cells freshly isolated from the peripheral blood of patients with cancer in concert with sensitive effector cell readout assays (such as the cytokine enzyme-linked immunospot assay) and MS to identify relevant peptide epitopes. In a model system, we have evaluated the capacity of natural Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell line-extracted peptides to activate "memory" viral-specific CD4(+) or CD8(+) T cells freshly isolated from the blood of an EBV-seropositive individual using the IFN-gamma enzyme-linked immunospot assay. After HPLC fractionation and loading onto autologous dendritic cells, multiple naturally processed HLA class I and II-associated lymphoblastoid cell line-derived peptides were isolated that were capable of inducing IFN-gamma spot production by "memory" T lymphocytes. Using MS analysis on a HPLC fraction recognized by CD8(+) T cells, we were able to sequence natural 9-, 10-, and 11-mer peptides naturally processed from the latent EBV antigen LMP-2 (latent membrane protein-2) and presented in the context of HLA-A2. This approach provides a useful methodology for the future identification of MHC-presented viral and tumor epitopes using freshly isolated patient materials.
CD4-Positive T-Lymphocytes↗
Assessment of autoimmunogenic potential of xenobiotics using the popliteal lymph node assay.
This article reviews the ability of the simple popliteal lymph node assay (PLNA) and variations thereof to assess the immunostimulating potential of low-molecular-weight xenobiotics, including pharmaceuticals. In essence, all variations of the PLNA detect the immune reaction in the popliteal lymph node to subcutaneous injection of a chemical into the footpad. The primary PLNA, in which the enlargement of popliteal lymph node is measured on injection of the chemical as such, can be regarded as a fast, simple, and reliable assay to detect and grade the immunostimulating potential of chemicals in a preclinical production phase. To prove T-cell sensitization, i.e., the involvement of T cells and/or induction of T-cell memory, secondary PLNAs or the so-called modified PLNA can be used. Secondary PLNAs can be performed in previously sensitized animals or by using adoptive T-cell transfer techniques. In the modified PLNA the well-defined reporter antigens TNP-ovalbumin and TNP-Ficoll are injected together with the chemicals and the number and isotype of the antibody-forming cells in the draining lymph node are analyzed. This modification of the PLNA enables definition of the involvement of T cells as well as type of immune response (T-cell sensitization vs mere inflammation as well as Th1 vs Th2) elicited by the chemical in an easy manner. To date, more than 100 chemicals have been tested in the PLNA and results indicate that all chemicals with documented adverse autoimmune or allergic effects in humans induce a positive PLN response. No false negatives have been found if metabolism is taken into consideration. It is important to realize that immunostimulation measured in the PLNA is only a first indication that a chemical can induce or exacerbate autoimmune(-like) disease.
Adjuvants, Immunologic↗