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PubMed2005

CD8 alpha alpha homodimer expression and role in CD8 T cell memory generation during influenza virus A infection in mice.

While the precise function of CD8alphaalpha homodimer expression on peripheral T cells is uncertain, recent evidence indicates that it facilitates survival and differentiation of lymphocytic choriomeningitis virus (LCMV)-specific memory CD8alphabeta T cell precursors in vivo. Here, we show that the CD8alphaalpha homodimer is also transiently up-regulated on influenza A virus-specific CD8alphabeta T cells after infection in vivo, temporally correlating with increased levels of the memory T cell development- and survival-related molecules IL-7Ralpha and Bcl-2, respectively. Unlike with LCMV, however, deletion of the CD8alphaalpha enhancer I does not abrogate CD8alphaalpha homodimer expression or manifest a significant impact on the generation of virus-specific, functional effector and central memory T cells in influenza A virus infection. These results demonstrate that the role of CD8alphaalpha in the generation of antiviral CD8 T cell memory is complex, presumably because various viral stimuli differentially regulate CD8alphaalpha expression. Further studies are needed to define those ligands that induce CD8alphaalpha on T cells during acute viral infections, and the general relevance of this process to memory T cell formation.

Animals↗

PubMed2002

Maintenance of serological memory by polyclonal activation of human memory B cells.

Production of antibodies can last for a lifetime, through mechanisms that remain poorly understood. Here, we show that human memory B lymphocytes proliferate and differentiate into plasma cells in response to polyclonal stimuli, such as bystander T cell help and CpG DNA. Furthermore, plasma cells secreting antibodies to recall antigens are produced in vivo at levels proportional to the frequency of specific memory B cells, even several years after antigenic stimulation. Although antigen boosting leads to a transient increase in specific antibody levels, ongoing polyclonal activation of memory B cells offers a means to maintain serological memory for a human lifetime.

Antibodies↗

PubMed2001

Direct comparison of prefrontal cortex regions engaged by working and long-term memory tasks.

Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes-no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e.g., FP-PFC in LTM retrieval).

Adult↗

PubMed2002

Maintenance and manipulation in spatial working memory: dissociations in the prefrontal cortex.

Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex. In Experiment I, memory set size for locations was parametrically varied, allowing for the assessment of BOLD signal across maintenance requirements. In the sec ond experiment, manipulation of spatial information held in working memory was contrasted with simple maintenance of that information. Both experiment evoked significant activity in a distributed spatia working memory network. Although dorsolateral prefrontal activation increased monotonically with memory set size, this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations. Activation in the superior frontal sulcal region was associated with maintenance of spatial information, increasing with memory se size. In contrast, ventrolateral prefrontal activation was present only at the highest memory set size, possibly due to the differential use of organizational strategies with more complex stimuli. These results sup port claims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region.

Algorithms↗

PubMed2005

Tissue trafficking patterns of effector memory CD4+ T cells in rheumatoid arthritis.

OBJECTIVE: Clonal populations of CD4+,CD28- T cells accumulating in rheumatoid arthritis functionally resemble end-differentiated, nondividing, short-lived effector memory cells that reside in peripheral tissues. We undertook this study to examine the tissue niche for CD4+,CD28- T cells and the signals regulating their survival and tissue homing patterns. METHODS: Chemokine receptor expression on CD4+,CD28- T cell clones and peripheral blood lymphocytes was assessed by multicolor cytometry. In vitro chemotaxis and transendothelial migration were examined in a Transwell system. In vivo tissue-homing patterns were established by adoptively transferring fluorescence-labeled T cell clones into SCID mice engrafted either with rheumatoid synovium or with human lymph nodes. RESULTS: CD4+,CD28- T cell clones adoptively transferred into human tissue-SCID mouse chimeras infiltrated rheumatoid synovium but preferentially homed to lymph nodes. Such T cells coexpressed the chemokine receptors CCR7, CCR5, and CXCR4 and migrated in response to both inflammatory chemokines (CCL5) and homing chemokines (CXCL12). T cell receptor crosslinking abrogated chemotactic responsiveness. In contrast, interleukin-12 stimulation induced the up-regulation of CCR5 and a shift in the in vivo homing pattern away from the lymph nodes toward the inflamed synovium. CONCLUSION: CD4+,CD28- T cells resemble both short-lived effector memory cells and long-lived central memory cells, and they find a niche both in inflamed synovium and in lymph nodes. Nonspecific cytokine stimulation, not antigen recognition, triggers the transition from the lymph node to the synovium. By maintaining CCR7 expression, these end-differentiated T cells can home to lymphoid organs, enhance their survival, support clonal expansion, and perpetuate autoreactivity.

Adoptive Transfer↗

PubMed1998

Cancer as a complex developmental disorder--nineteenth Cornelius P. Rhoads Memorial Award Lecture.

The processes of differentiation and tumorigenesis have been long thought to be connected. The recent identification of Patched, a gene essential for Drosophila embryonic development, as a tumor suppressor has focused attention on the concept that tumorigenesis involves abnormalities of development. In fact, a large number of genes in the signalling pathway of the Patched gene are either tumor suppressors or oncogenes. This supports the concept that growth control is a critical requirement of differentiation, and that aberrant cellular development can contribute to malignancy. Whereas the identification of genes that result in dominantly inherited cancer syndromes has played a vital role in understanding cancer, the vast majority of "sporadic" cancers have properties of a complex genetic disease. Approaches to identify common alleles in cancer-associated genes promise to increase our understanding of the disease and aid the rational design of preventative and therapeutic strategies.

Animals↗

PubMed2003

Classical olfactory conditioning in the cockroach Periplaneta americana.

We established a classical conditioning procedure for the cockroach, Periplaneta americana, by which odors were associated with reward or punishment. Cockroaches underwent differential conditioning trials in which peppermint odor was associated with sucrose solution and vanilla odor was associated with saline solution. Odor preference of cockroaches was tested by allowing them to choose between peppermint and vanilla sources. Cockroaches that had undergone one set of differential conditioning trials exhibited a significantly greater preference for peppermint odor than did untrained cockroaches. Memory formed by three sets of differential conditioning trials, with an inter-trial interval of 5 min, was retained at least 4 days after conditioning. This conditioning procedure was effective even for cockroaches that had been harnessed in plastic tubes. This study shows, for the first time in hemimetaborous insects, that both freely moving and harnessed insects are capable of forming olfactory memory by classical conditioning procedure. This procedure may be useful for future electrophysiological and pharmacological studies aimed at elucidation of neural mechanisms underlying olfactory learning and memory.

Animals↗

PubMed2004

Sex differences and correlations in a virtual Morris water task, a virtual radial arm maze, and mental rotation.

Different tasks are often used to assess spatial memory in humans compared to nonhumans. In order to bridge this paradigmatic gap, we used a within-subject design to test 61 undergraduates on three spatial memory tasks. One of these tasks, the Vanderberg 3D mental rotation task, is classically used to assess spatial memory in humans. The other two tests are virtual analogues of two tasks used classically to assess spatial memory in rodents: the Morris water task and an eight-arm radial maze. We find that males perform significantly better than females on the mental rotation task and in finding a hidden platform in the virtual Morris water task. Moreover, during a probe trial, males spend significantly more distance of their swim in the training quadrant, but males and females do not differ in navigating to a visible platform. However, for the virtual eight-arm radial maze, there is no sex difference in working memory errors, reference memory errors, or distance to find the rewards. Surprisingly, an examination of the correlations among the three tasks indicates that only mental rotation ability and Morris water task probe trial performance correlate significantly among the three tasks (i.e. there are no significant correlations with traditional measures the tasks, e.g. time or distance to completion). Hence, the Morris water task and the eight-arm radial maze do not assess spatial memory in the same manner, and even after equating factors such as motivation, stress, and motor demands, there still are procedural demands of the tasks that reinforce differential strategy selection during spatial memory. This suggests that caution should be taken when utilizing these two tasks interchangeable as tests of spatial memory.

Adolescent↗

PubMed1988

Increased immunoglobulin E Fc receptor bearing cells in germinal centers of hyperimmunoglobulinemia E patients.

Lymph nodes from 6 patients with hyperimmunoglobulinemia E (hyper-IgE; 4 with Kimura's disease, 1 with atopic dermatitis, and 1 with immunoblastic lymphadenopathy-like T cell lymphoma) and from 7 patients with normal IgE levels were studied to determine the localization of dendritic reticulum cells and of cells bearing Fc epsilon and C3d receptors and immunoglobulin E. The avidin-biotin-glucose oxidase method was used for unfixed biopsy specimens. To identify the above-mentioned cells, H107, a murine monoclonal antibody specific to the Fc epsilon receptor molecule, and corresponding antibodies specific to the other cell types were used. In 5 hyper-IgE patients (4 with Kimura's disease and 1 with atopic dermatitis) all germinal centers of the lymph nodes showed heavy reticular staining with H107, the dendritic reticulum cells being most intensely stained. In contrast, the germinal centers of the lymph nodes in the 7 patients with a normal IgE level only lightly or partially stained with H107. The staining pattern of anti-IgE was similar to that of H107 in the hyper-IgE cases. Likewise, C3d receptor and dendritic reticulum cell-related antigens were demonstrated very intensely in all germinal centers in lymph nodes of patients with hyper-IgE and normal IgE levels. These findings suggest that in a hyper-IgE state increased numbers of dendritic reticulum cells in a germinal center express the Fc epsilon receptor and that such cells may play a role in the differentiation of IgE-producing memory B cells.

Angiolymphoid Hyperplasia with Eosinophilia↗

PubMed2003

In vitro differentiation from naive to mature E-selectin binding CD4 T cells: acquisition of skin-homing properties occurs independently of cutaneous lymphocyte antigen expression.

We previously showed that skin-homing CD4 T cells in peripheral blood can be subdivided into three populations on the basis of the expression pattern of the cutaneous lymphocyte Ag (CLA) and fucosyltransferase VII (FucT-VII): FucT-VII(+)CLA(-), FucT-VII(+)CLA(+), and FucT-VII(-)CLA(+). In view of the known late appearance of CLA during T cell differentiation, T cells programmed to attain skin-homing properties may start to generate E-selectin-binding epitopes at early stages of differentiation before induction of CLA expression. To this end, the in vitro differentiation from naive to CLA(+) memory T cells was followed after activation with anti-CD3 mAb. Here we demonstrate that naive skin-homing CD4 T cell precursors undergo a linear differentiation process from the FucT-VII(+)CLA(-) phenotype to the FucT-VII(+)CLA(+) phenotype and eventually to the FucT-VII(-)CLA(+) phenotype. The appearance of the FucT-VII(+)CLA(-) subset coincided with or could be immediately followed by the generation of E-selectin binding epitopes, and even after E-selectin-binding epitopes were no longer detectable, CLA remained expressed for prolonged periods of time, suggesting that induction of functional E-selectin ligands depends primarily on the expression of FucT-VII, but not CLA. Immunofluorescence and confocal microscopy studies of these T cells confirm that most E-selectin ligands were found independently of CLA expression.

Adult↗

PubMed2003

Alzheimer's disease versus normal ageing: a review of the efficiency of clinical and experimental memory measures.

This paper reviews research findings concerning memory performance in Alzheimer's disease (AD) and normal ageing. Studies using clinical (i.e., episodic) memory tests are compared with studies using various experimental memory paradigms (semantic memory, implicit memory, working memory), in order to determine their efficiency to differentiate between AD and normal ageing. In addition, attention is focused on early and preclinical AD. It is argued that traditional clinical memory tests alone are not best able at detecting AD at an early stage. More specifically, tasks calling upon semantic knowledge may aid to an earlier and more efficient assessment of AD.

Aging↗

PubMed2004

How do we avoid developing allergy: modifications of the TH2 response from a B-cell perspective.

The synthesis of IgE by B cells occurs at a low rate compared with that of other antibodies, even in allergic subjects. One rate-limiting step is the class switch, by which B lymphocytes switch to produce immunoglobulin epsilon heavy chains rather than micro or gamma heavy chains. We propose an additional rate-limiting step: survival of the B lymphocyte after the switch to IgE. The hypothesis we present here is that the survival of the IgE-switched B cell is compromised, particularly in an active germinal center. Antigenic stimulation in the absence of a danger signal fails to induce a mature germinal center, which allows IgE-switched B cells to escape and mature into plasma cells. Antigenic stimulation in the presence of a danger signal (or under nonhygienic conditions) induces germinal centers, which eliminate IgE-switched B cells. Thus the essence of an allergen is antigenic stimulation in the absence of conditions that generate mature germinal centers. Because germinal centers are important for the generation of B-cell memory, the IgE immune response is characteristically poor in memory (but might be long lasting because of the generation of long-lived plasma cells). In addition to this direct route to IgE, typical for atopic sensitization, another type of T(H)2 response exists. On chronic allergen exposure with the concomitant induction of germinal centers, IgG4-switched B memory cells are induced that are slow to differentiate into plasma cells. These IgG4-switched B memory cells might occasionally undergo a secondary switch to IgE.

Allergens↗

PubMed1984

Inducer-mediated commitment of murine erythroleukemia cells to terminal cell division: the expression of commitment.

Murine erythroleukemia cells (MELC) are transformed cells that can be induced to differentiate by a variety of agents, such as hexamethylenebisacetamide (HMBA) and dimethyl sulfoxide. Dexamethasone suppresses HMBA-mediated MELC differentiation, but MELC retain a memory for their exposure to HMBA since, on transfer from culture with HMBA and dexamethasone to medium without additions, a portion of the cells express characteristics of terminal differentiation. This study characterizes the steroid suppressed steps in the multi-step process of inducer-mediated MELC terminal differentiation. MELC in culture with HMBA and dexamethasone show low levels of commitment to terminal cell division; upon transfer to culture with inducer alone there is a rapid increase in the proportion of committed cells. The magnitude of this rapid or "step-up" expression of commitment increased with the length of prior culture with inducer and steroid. This step-up expression is not inhibited by actinomycin D or cordycepin but is blocked by cycloheximide. HMBA is required for step-up expression of commitment. In the absence of inducer, there is a rapid decay in the capacity for step-up expression. Thus, HMBA initiates a series of changes leading to the accumulation of factors--which may be mRNAs--whose expression is blocked by dexamethasone. Hemin, which induces MELC accumulation of globin mRNA but not commitment to terminal cell division, cannot, as does HMBA or dimethyl sulfoxide, cause step-up expression of commitment.

Acetamides↗

PubMed1982

Constructive processes in skilled and less skilled comprehenders' memory for sentences.

An experiment was carried out to investigate seven-eight-year-old children's memory for aurally presented sentences. A recognition-memory task was used to probe constructive memory processes in two groups differentiated by their ability at comprehending printed text. The recognition errors of both groups indicated that they constructed meanings implied by the original input sentences, whilst demonstrating poor memory for the syntactic form of the sentences. The tendency to construct meanings implied by the original input sentences was greater in children who scored higher on tests of reading comprehension of test. These results indicate that constructive memory processes are related to comprehension ability in young readers.

Child↗

PubMed2004

Gene-specific timing and epigenetic memory in oocyte imprinting.

Imprinted genes are differentially marked during germ cell development to allow for their eventual parent-of-origin specific expression. A subset of imprinted genes becomes methylated during oocyte growth in both mouse and human. However the timing and mechanisms of methylation acquisition are unknown. Here, we examined the methylation of the Snrpn, Igf2r, Peg1 and Peg3 differentially methylated regions in postnatal growing mouse oocytes. Our findings indicate that methylation was acquired asynchronously at these different genes. Further analysis of Snrpn DMR1 revealed that parental alleles retain an epigenetic memory of their origin as the two alleles were recognized in a parental-specific manner in the absence of DNA methylation. In addition, we show that methylation acquisition was probably related to oocyte diameter and coincided with the accumulation of Dnmt3a, Dnmt3b and Dnmt3L transcripts. Methylation of the repetitive retroviral-like intracisternal A particle also occurred during this same window of oocyte growth. These findings contribute to our understanding of the epigenetic mechanisms underlying imprint acquisition during female germ cell development and have implications for the practice of assisted reproductive technologies.

Animals↗

PubMed2005

Feature binding in perceptual priming and in episodic object recognition: evidence from event-related brain potentials.

It is argued that explicit remembering is based on so-called episodic tokens binding together all perceptual features of a visual object. In episodic recognition, these features are collectively reactivated. In support of this view, it has been shown that changing sensory features of a stimulus from study to test decreases subject's performance in an episodic recognition task, even though the changed features are irrelevant for the recognition judgment. On the other hand, repetition priming is unaffected by such manipulations of perceptual specificity. Implicit memory performance is therefore thought to depend on structural representations, so-called types, comprising only invariant perceptual features, but no exemplar-specific details. Event-related potentials (ERPs) in our study revealed electrophysiological evidence for the differential involvement of these perceptual memory traces in explicit and implicit memory tasks. Participants attended either a living-nonliving task or an episodic recognition task with visually presented objects. During test both groups of participants processed new objects and old objects, which were repeated either identically or in a mirror-reversed version. In the implicit task ERPs showed an occipitoparietal repetition effect, which was the same for identically repeated items and mirror reversals. In contrast, in the explicit task an early mid-frontal old/new effect for identical but not for mirror-reversed old objects was observed indicating involuntary access to perceptual information during episodic retrieval. A later portion of the old/new effect solely differentiated both types of old items from new ones.

Adult↗

PubMedDate not supplied

Problems in the differential diagnosis of choroidal nevi and malignant melanoma. XXXIII Edward Jackson Memorial lecture.

Failure to appreciate the variability in the natural course of choroidal nevi (benign melanomas) has caused the adoption of a misleading cytologic classification of malignant melanomas. This classification is not based on adequate clinical observation, reliable cytologic criteria for malignancy, or sufficient autopsy information. The available evidence suggests that spindle A tumors are benign and that spindel B tumors, although capable of local destruction of the eye, metastasize infrequently. The risk of observation of small melanocytic tumors must be weighed against the risk that early enucleation or other forms of therapy may not favorably affect prognosis. The clinical observations to date at the Bascom Palmer Eye Institute indicate that the risks of observation are low.

Adult↗

PubMed1998

Fuzzy-trace theory and false memory: new frontiers.

We describe the origins of fuzzy-trace theory, including Piagetian, interference, information-processing, and judgment and decision-making influences. The contrasting properties of gist and verbatim memory serve as its foundation and, in recent models of spontaneous and implanted false memories, explain seemingly contradictory developmental trends, such as reverse developmental findings, differential time courses for true and false memories, and conflicting effects of trace strength. However, approaches that integrate fuzzy-trace theory with neurological, social, emotional, and motivational perspectives are needed. A method for accomplishing this integration, using the recent models, is introduced and new research that spans these perspectives is discussed. Relations to other contemporary theories, especially source-monitoring and dual-process theories, are also explained. We conclude by rejecting the notion that spontaneous false memories are actually "true" and distinguish gist and verbatim senses of the term "true" that have different consequences in real life.

Humans↗