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PubMed2002

Cellular and molecular requirements for the recall of IL-4-producing memory CD4(+)CD45RO(+)CD27(-) T cells during protection induced by attenuated Plasmodium falciparum sporozoites.

The requirements for maintenance of antigen (Ag)-specific memory T cells in protection to malaria is poorly understood. We have previously demonstrated a recall of IL-4-producing memory CD4(+)CD45RO(+) T cells with parasitized red blood cells (pRBC) in persons protected by radiation-attenuated Plasmodium falciparum sporozoites (gamma-spz). Using the CD27 marker, we have now identified two subsets of CD4(+)CD45RO(+) T cells: CD4(+)CD45RO(+)CD27(+) T cells representing an early memory and CD4(+)CD45RO(+)CD27() T cells representing a terminally differentiated memory cells. A small subset of CD4(+)CD45RO(+)CD27(-) T cells also expressed CD70, the CD27 ligand. The addition of anti-CD70 monoclonal antibody (mAb) to pRBC-stimulated cultures significantly inhibited the conversion of CD27(+) to CD27(-) subset without profoundly affecting IL-4 production. In contrast, the inclusion of anti-CD27 mAb in parallel cultures abrogated IL-4 production without interfering with conscription of T cells into the CD27(-) T cell set. We propose that the persistence of memory CD4(+) T cells depends on Ag-driven conscription of a mature memory phenotype through co-ligation of CD27 and CD70 expressed, respectively, on CD27(+) and CD27(-) T cells. Hence, protracted protection in malaria depends in part on memory CD4(+) T cells that require specific Ag presumably from the repositories of liver-and blood-stage antigens and the delivery of a second signal from the CD27:CD70 interaction.

Adult↗

PubMedDate not supplied

Word list versus story memory in Alzheimer disease and frontotemporal dementia.

Memory impairment, characterized by a pattern of rapid forgetting, is the hallmark deficit in Alzheimer's disease (AD). Memory deficits have also been reported in frontotemporal dementia (FTD), and are thought to reflect diminished organizational and attentional abilities leading to a pattern of decreased acquisition of new information. The present study compared patients with AD, the behavioral variant of FTD, and cognitively intact elderly control subjects on two types of memory tests: story memory and word list recall. The percent of information recalled immediately (encoded), after a delay, and the percent retention between these conditions was calculated for both tests. The results showed that FTD patients encoded and recalled more information from the story than AD patients. No difference was found between FTD and AD patients for encoding of the word list. However, FTD patients recalled more words after a delay than AD patients. Percent retention on both tasks was also greater for the FTD group. The results suggest that patterns of performance on different tests of memory, and, in particular, measures of retention, can be useful in differentiating memory impairment in AD from that of FTD on cognitive testing.

Aged↗

PubMed1999

Altered memory T cell differentiation in patients with early rheumatoid arthritis.

The chronic immune response in rheumatoid arthritis (RA) might be driven by activated Th1 cells without sufficient Th2 cell differentiation to down-modulate inflammation. To test whether disordered memory T cell differentiation contributes to the typical Th1-dominated chronic inflammation in RA we investigated differentiation of resting CD4+ memory T cells in patients with early (6 wk to 12 mo) untreated RA and in age- and sex-matched healthy controls in vitro. No difference in cytokine secretion profiles of freshly isolated memory T cells was detected between patients and controls. A cell culture system was then employed that permitted the differentiation of Th effectors from resting memory T cells by short term priming. Marked differences were found in response to priming. Th2 cells could be induced in all healthy controls by priming with anti-CD28 in the absence of TCR ligation. By contrast, priming under those conditions resulted in Th2 differentiation in only 9 of 24 RA patients. Exogenous IL-4 could overcome the apparent Th2 differentiation defect in seven patients but was without effect in the remaining eight patients. In all patients a marked decrease in IL-2-producing cells and a significant increase in well-differentiated Th1 cells that produced IFN-gamma but not IL-2 were evident after priming with anti-CD3 and anti-CD28. The data suggest that CD4+ memory T cells from patients with early untreated RA manifest an intrinsic abnormality in their ability to differentiate into specific cytokine-producing effector cells that might contribute to the characteristic Th1-dominated chronic (auto)immune inflammation in RA.

Adult↗

PubMed2005

Neuropsychological characteristics of children with the 22q11 Deletion Syndrome: a descriptive analysis.

Previous reports of cognitive functioning in children with the 22q11 Deletion Syndrome have reported marked variability in IQ and achievement subtest scores. Studies have begun to explore neuropsychological function in 22q11 DS however results are inconsistent and the profile incomplete. We assessed 40 children ages 5-12 with 22q11 DS. Consistent with past results, visual-spatial memory was significantly lower than verbal memory. Differentially lowered scores were found only in visual attention, working memory and motor function. Contrary with some past results quantitative, verbal ability, and visual spatial memory scores were within 1 SD from the standardization sample mean. Motor behavior, not typically discussed with regard to 22q11 DS school-age children, may be critical to incorporate in neurocognitive studies of children with 22q11 DS. Implications of these findings are considered with regard to past results.

Brain↗

PubMed1987

Mentally retarded and nonretarded subjects' long-term recognition memory.

Mentally retarded and nonretarded teenagers' long-term recognition for faces was compared. Initially, subjects viewed 255 face pictures, with multiple exposures of some pictures provided to equate immediate memory for the groups for a portion of the data. The majority of the subjects were then tested immediately and after 1 day and 1 week using a forced-choice method. The retarded subjects performed at a lower overall level than did the nonretarded subjects, there was significant memory loss across the retention intervals, and there was no differential memory loss between the groups. A 6-month follow-up retention test revealed no further memory differences. Results suggest that long-term memory is unrelated to intelligence level.

Adolescent↗

PubMed1998

Memory monitoring by animals and humans.

The authors asked whether animals and humans would use similarly an uncertain response to escape indeterminate memories. Monkeys and humans performed serial probe recognition tasks that produced differential memory difficulty across serial positions (e.g., primacy and recency effects). Participants were given an escape option that let them avoid any trials they wished and receive a hint to the trial's answer. Across species, across tasks, and even across conspecifics with sharper or duller memories, monkeys and humans used the escape option selectively when more indeterminate memory traces were probed. Their pattern of escaping always mirrored the pattern of their primary memory performance across serial positions. Signal-detection analyses confirm the similarity of the animals' and humans' performances. Optimality analyses assess their efficiency. Several aspects of monkeys' performance suggest the cognitive sophistication of their decisions to escape.

Adaptation, Psychological↗

PubMed1992

Beliefs about memory changes across the adult life span.

Beliefs about age-related differences in memory were examined with an adaptation of the Short Inventory of Memory Experiences. In Experiment 1, 142 adults (mean age = 36 years) reported significantly more positive expectations for memory in everyday life for persons aged 25 years than for those aged 70 years. In Experiment 2, a between-subjects design with 189 adults (mean age = 34 years) was employed to examine the generality of memory beliefs about age-related change and the anticipated slope. Beliefs about the memory of 25-year-olds were significantly more positive than for 45- and 65-year-olds, which were correspondingly higher than for 85-year-olds. Secondary regression analyses revealed that participants with good memory self-perceptions anticipated better memory performance for others overall. In addition, older respondents exhibited more differentiated memory beliefs across age groups than younger respondents, especially at the two younger target ages. Examination of age-based memory beliefs with this type of instrument provides a new opportunity to integrate cognitive and social psychological approaches to the study of memory in aging.

Adolescent↗

PubMed1999

Distribution of human CMV-specific memory T cells among the CD8pos. subsets defined by CD57, CD27, and CD45 isoforms.

Chronic antigenic stimulation has been associated with peripheral blood expansions of CD8pos. T cells characterized by CD57 expression, loss of CD27 expression, and reversal of the CD45RO(bright) /RA(dim) phenotype usually associated with immunological memory towards a CD45RO(dim) /RA(bright) phenotype. However, the relationship and functional significance of these subset(s) has remained controversial. Here, this issue was addressed using a novel flow cytometric technique that allows simultaneous detection of human cytomegalovirus (HCMV)-specific CD8pos. memory T cells by rapid (< 6 h) HCMV peptide-specific induction of cytokine synthesis, and their phenotypic characterization, including CD57, CD27 and CD45RA/RO. The vast majority of resting CD8(pos.) T cells capable of rapid induction of IFN-gamma and TNF-alpha synthesis in response to HCMV peptides were found in a subset characterized by intermediate to high expression of CD57, down-regulation/loss of CD27, and varying degrees of reversal of the classical "memory" CD45RO(bright) /RA(dim) phenotype. This subpopulation likely includes the fully differentiated memory cells responsible for the long-term immune defense against HCMV reactivation.

Antigens, CD↗

PubMed2004

T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis.

Identification of T-cell subsets that are infected in vivo is essential to understanding the pathogenesis of human immunodeficiency virus (HIV) disease; however, this goal has been beset with technical challenges. Here, we used polychromatic flow cytometry to sort multiple T-cell subsets to 99.8% purity, followed by quantitative PCR to quantify HIV gag DNA directly ex vivo. We show that resting memory CD4(+) T cells are the predominantly infected cells but that terminally differentiated memory CD4(+) T cells contain 10-fold fewer copies of HIV DNA. Memory CD8(+) T cells can also be infected upon upregulation of CD4; however, this is infrequent and HIV-specific CD8(+) T cells are not infected preferentially. Naïve CD4(+) T-cell infection is rare and principally confined to those peripheral T cells that have proliferated. Furthermore, the virus is essentially absent from naïve CD8(+) T cells, suggesting that the thymus is not a major source of HIV-infected T cells in the periphery. These data illuminate the underlying mechanisms that distort T-cell homeostasis in HIV infection.

Adult↗

PubMed1998

Human memory T cell differentiation into Th2-like effector cells is dependent on IL-4 and CD28 stimulation and inhibited by TCR ligation.

Freshly isolated memory T cells primarily produced IL-2 and small amounts of IL-4 and IFN-gamma after stimulation in vitro. Priming for 5 days in vitro with anti-CD28 monoclonal antibodies (mAb) alone markedly increased production of IL-4. In comparison to fresh cells, the increase in the amount of IL-4 secreted reflected a marked increase in the number of IL-4-producing cells. Stimulation with immobilized anti-CD3 mAb during priming limited subsequent IL-4 production. By contrast, IFN-gamma production from in vitro primed memory T cells was directly correlated to the concentration of priming anti-CD3 mAb. IL-2 production by all restimulated cells was decreased. The differentiation of IL-4-producing cells could be blocked by antibody to IL-4 and enhanced by the addition of recombinant IL-4 as well as antibody to IFN-gamma. Of note, the IL-4-producing effector cells induced from in vitro priming derived from the early CD27pos memory T cell subset, whereas the small CD27neg differentiated memory subset produced IL-4 without in vitro priming. The results indicate that memory T cells can be directed to differentiate into IL-4-producing effector cells by stimulation via CD28 and IL-4, whereas increasing engagement of the TCR limits Th2 memory cell differentiation.

Antibodies, Monoclonal↗

PubMed2003

Cutting edge: effector memory CD8+ T cells in the lung airways retain the potential to mediate recall responses.

Previous studies have shown that long-lived memory CD8(+) T cells persist in the lung airways following the resolution of a murine Sendai virus infection. These cells are CD11a(low), noncytolytic, and do not proliferate in the lung airways raising the possibility that they are "end stage" or terminally differentiated memory cells. In this current report, we investigated the functional characteristics of these cells by analyzing their capacity to respond to secondary viral infection outside of the lung environment. We show that, after transfer into the bloodstream, CD11a(low) memory T cells from the lung airways can return to the secondary lymphoid tissue and respond to a secondary viral challenge. Furthermore, these cells re-express CD11a, which may contribute to their migratory and proliferative capacity. These data demonstrate that lung airway memory CD8(+) T cells are not terminally differentiated cells and retain the capacity to mediate recall responses to infection.

Animals↗

PubMed1998

Developmental changes and functional properties of human memory T cell subpopulations defined by CD60 expression.

The present study was undertaken to examine developmental changes of T cells expressing CD60 and their functional properties. Three-color immunofluorescence analysis revealed that the CD60 antigen was preferentially expressed on a proportion of memory (CD45RO+) CD4+ T cells, but less on memory CD8+ T cells, while this antigen is undetectable in naive (CD45RO-) T cells. A frequency of memory CD4+ T cells expressing CD60 in the peripheral blood was negligible in newborns and gradually increased with advancing age. CD60+ memory CD4+ T cells showed stronger proliferative responses to PPD and produced higher levels of IL-4 and IL-10 than CD60- ones, whereas production of IL-2 and IFN-gamma was similarly found in both cell subpopulations. In addition, it was shown that efficient helper activity for Ig production by B cells was predominated in CD60+ memory CD4+ T cells. These results suggest that CD60 may be primarily expressed on the functionally differentiated memory effector cells among circulating CD45RO+ CD4+ T cells.

Adolescent↗

PubMed1998

The subjective organization of input and output events in memory.

In order to study the organization of memory for self-performed actions, 80 participants were presented with 20 action phrases for ten consecutive study-test cycles. Enactment was manipulated both in the input phase and in the output phase by having participants say or enact the phrases during encoding and/or during testing. Enactment at input or output generally enhanced both the quantity and the accuracy of recall and also improved output monitoring. More important, subjective organization, as indexed by the tendency to recall the same two phrases successively across repeated recall tests, was significant for all conditions, even on the first pair of trials, and increased systematically with repeated study-test cycles. Enactment neither impaired nor enhanced the amount of organization, and in all conditions a positive correlation was obtained between recall and subjective organization. Some commonalities in the nature of memory organization were found across all conditions. The results suggest that enactment may lead to more differentiated memory traces, resulting in more accurate recall. Although subjective organization was clearly observed when enactment was involved, its contribution to the enhancement of recall deserves further examination.

Adult↗

PubMed2000

An electrophysiological test of directed forgetting: the role of retrieval inhibition.

A central issue in the research of directed forgetting is whether the differential memory performance for to-be-remembered (TBR) and to-be-forgotten (TBF) items is solely due to differential encoding or whether retrieval inhibition of TBF items plays an additional role. In this study, recognition-related event-related brain potentials (ERPs) were used to examine this issue. The spatio-temporal distributions of the old/new ERP effects obtained in Experiment 1 that employed a directed forgetting paradigm were compared with those recorded in Experiment 2 in which the level of processing was manipulated. In Experiment 1, participants were instructed to remember or to forget words by means of a cue presented after each word. ERPs recorded in the recognition test revealed early phasic frontal and parietal old/new effects for TBR items, whereas TBF items elicited only a frontal old/new effect. Moreover, a late right-frontal positive slow wave was more pronounced for TBF items, suggesting that those items were associated with a larger amount of post-retrieval processing. In Experiment 2, the same cueing method and the same stimulus materials were used, and memory encoding was manipulated by cueing participants to process the words either deeply or shallowly. Both deeply and shallowly encoded items elicited phasic frontal and parietal old/new effects followed by a late right-frontal positive slow wave. However, in contrast to TBR and TBF items, these effects differed only quantitatively. The results suggest that differential encoding alone cannot account for the effects of directed forgetting. They are more consistent with the view that items followed by an instruction to forget become inhibited and less accessible, and, therefore, more difficult to retrieve.

Adult↗

PubMed2005

Mucosal effector memory T cells: the other side of the coin.

Immunological memory allows for rapid and effective protective immunity to previously encountered pathogens. New insights in understanding specific memory differentiation and function have now indicated that in addition to providing enhanced immunity, an important purpose of immunological memory is to provide immediate protection at all sites of the body, including non-lymphoid tissues. Effector memory CD8 T cells have the capacity to reside long-term at epithelial surfaces, where they allow for rapid containment of the invading pathogens at the local entry site and prevent systemic spreading and excessive immune responses. The accumulation of tissue-specific memory T cell subsets, together with cross-reactivity of these antigen-experienced T cells even to unrelated pathogens, provides flexibility and expansion of their specificity repertoire that over time greatly surpasses that of the declining naïve T cell populations. This review will discuss new insights into T cell memory. We will focus in particular on the generation and function of effector memory CD8 T cells at the intestinal mucosa, which represents one of the largest entry sites for pathogens.

Animals↗

PubMed1996

Assessing declarative memory in schizophrenia using Wisconsin Card Sorting Test stimuli: the Paired Associate Recognition Test.

The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophrenia-specific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.

Adult↗

PubMed2006

Brain responses of explicit and implicit memory: An event-related potential study.

Implicit memory is acquired by an unintentional or unconscious learning. Recognition memory involves either automatic knowing or consciously controlled remembering. We provided an event-related potential paradigm capable of differentiating memory for the explicitly learned, implicitly learned and unstudied materials. In the explicit memory, we obtained both frontal (controlled retrieval) and parietal (recollection) old/new effects. In the implicit memory, we found persistent occipitotemporal activation (visual priming) and late attenuation in the temporoparietooccipital (repetition suppression). Event-related potential provides an insight into the dissociable mechanism of memory function that supports the dual process model with an enhanced temporal resolution on the dynamic process of both explicit perceptual learning and implicit perceptual priming.

Adult↗

PubMed2006

Stimulation history dictates memory CD8 T cell phenotype: implications for prime-boost vaccination.

Heterologous prime-boost vaccination results in increased frequencies of memory T cells. Although these quantitative effects of reexposure to Ag are well documented, little is known about the impact of boosting on the functional qualities of memory T cells. To address this critical issue, we have used three different types of immunization regimens and examined how boosting effects the function and anatomic location of memory CD8 T cells. We found that memory T cell phenotype differed substantially depending on the number of immunizations and that secondary and tertiary responses resulted in the generation of memory CD8 T cells that retained effector-like properties and showed preferential accumulation in nonlymphoid tissues. These results show that memory differentiation is coupled to the history of Ag experience and that prime-boost vaccination strategies have important consequences on memory CD8 T cell quality and surveillance within mucosal tissues.

Animals↗