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PubMedDate not supplied

In search of the neurobiological underpinnings of the differential outcomes effect.

Correlating unique rewards with to-be-remembered events (the Differential Outcomes Procedure [DOP]) enhances learning and memory performance in a range of species. Recently, we have demonstrated that the DOP can be used to reduce or eliminate the learning and memory impairments associated with animal models of amnesia and dementia. This powerful phenomenon, the Differential Outcomes Effect (DOE), has led to the question: How does such a simple manipulation exert such dramatic influence on learning and memory performance? A revised two-process account of the DOE states that using the DOP results in the activation of reward expectancies through Pavlovian mechanisms. The use of unique reward expectancies alters the nature of cognitive processing used to solve discrimination tasks. The change in cognitive processing is represented by utilization of a different memory system than that commonly used to acquire and remember information when a Nondifferential Outcomes Procedure (NOP) is used. Using neurochemical manipulations, it has been demonstrated that different, potentially independent, brain systems modulate memory performance when subjects are trained with a NOP versus a DOP. This memory-based DOP/NOP distinction resembles other dissociative memory theories in which two psychological processes are purportedly served by distinct neurobiological mechanisms. In addition, such results have important ramifications for the treatment of memory disorders because they demonstrate that stimulus and behavioral manipulations, like drugs, can influence neurotransmitter functioning.

Aging↗
PubMed1994

CNS roles in implementation of a differentiated case management model.

As advanced nursing practitioners and consultants, CNSs are leaders in affecting changes in nursing practice. During implementation of Primm's model of differentiated case management at Community Memorial Hospital, Menomonee Falls, Wisconsin, the CNSs enacted the roles of implementation consultant, researcher, direct care provider, educator, and performance and project evaluation consultant. The CNSs were committed to initiating and maintaining change, and facilitating momentum to incorporate the differentiated levels of staff nurse practice. We describe CNS roles in this process as well as outcomes seen after implementation of differentiated case management.

Education, Nursing, Continuing↗
PubMed1998

Estrogen and memory in a transsexual population.

The association between administered estrogen and performance on verbal memory and other cognitive tasks was examined. Male-to-female transsexuals undergoing estrogen treatment for sex reassignment (n = 29) scored higher on Paired Associate Learning (PAL) compared to a similar transsexual control group, awaiting estrogen treatment (n = 30) (P < 0.05). No differences between groups receiving and not receiving estrogen were detected on a control memory task (Digit Span) or on other cognitive tasks including Mental Rotations and Controlled Associations. There were no group differences in age. Group differences in mood or in general intellectual ability also did not explain the findings. Results suggest a specific influence of estrogen in men on verbal memory tasks, similar to that seen in prior studies of women. They are discussed in terms of differential processing demands of the two memory tasks and possible differences between estrogenic influences on Mental Rotations and Controlled Associations in men versus women.

Adult↗
PubMed2000

Low reliability of perceptual priming: consequences for the interpretation of functional dissociations between explicit and implicit memory.

In this study, three experiments are presented that investigate the reliability of memory measures. In Experiment 1, the well-known dissociation between explicit (recall, recognition) and implicit memory (picture clarification) as a function of age in a sample of 335 persons aged between 65 and 95 was replicated. Test-retest reliability was significantly lower in implicit than in explicit measures. In Experiment 2, parallel-test reliabilities in a student sample confirmed the finding of Experiment 1. In Experiment 3, the reliability of cued recall and word stem completion was investigated. There were significant priming effects and a dissociation between explicit and implicit memory as a function of levels of processing. However, the reliability of implicit memory measures was again substantially lower than in explicit tests in all test conditions. As a consequence, differential reliabilities of direct and indirect memory tests should be considered as a possible determinant of dissociations between explicit and implicit memory as a function of experimental or quasi-experimental manipulations.

Adult↗
PubMed1990

Special differentiation requirements of original and enriched secondary cytotoxic T lymphocyte precursors (pCTL-2 memory cell) specific for the class I histocompatibility molecule.

The in vivo-induced pCTL-2 cells of the L3T4- Lyt-2+ phenotype specific for the H-2Kb molecule are converted into effector CTLs in mixed lymphocyte culture (MLC) in the presence of heat-treated donor stimulators much more efficiently when the donor and recipient differ from each other, not only in the major histocompatibility complex (MHC) class I (H-2Kb) (anti-B10.MBR B10.AKM) but also in the MHC classes I + II, i.e., Kb + Ib (anti-C57BL/6 B10.D2 (R101)). The differentiation of original pCTL-2 is enhanced as the result of a synergistic action of the Kb alloantigen and rIL-2 in small doses. The anti-Kb pCTL-2, after their separation from helper T cells non-adherent to the macrophage donor monolayer and their subsequent elution from it, give rise to pronounced differentiation in simplified conditions over 3 days in monoculture in the absence of both stimulators and rIL-2. It is suggested that spontaneous and highly efficient specific differentiation of the eluted pCTL-2 is due to a dramatically enhanced secretion of the CTL differentiation factor by pCTL-2 themselves, and in addition, rIL-2 can also contribute to the secretion of this factor.

Animals↗
PubMed2005

Memory T cell homeostasis and senescence during aging.

Human memory T cell pools proliferate and differentiate at varying rates that are determined by the frequency of lifelong antigenic re-encounter with different specific antigens. An important question concerning immunity is whether certain specific pools of memory T cells are driven to exhaustion in elderly subjects, a pertinent point in view of increasing human life expectancy. An emerging consensus is that cytomegalovirus (CMV), a beta-herpesvirus with a prevalence of 60-90% worldwide, is an agent that induces specific T cells to extreme differentiation. The question that begs to be answered is whether this can explain why CMV seropositivity and the presence of highly differentiated CMV-specific T cells are included in a cluster of immune parameters that have been shown recently to predict the early mortality of elderly humans.

Aging↗
PubMed2005

CD4-CD8- T cells control intracellular bacterial infections both in vitro and in vivo.

Memory T cells, including the well-known CD4(+) and CD8(+) T cells, are central components of the acquired immune system and are the basis for successful vaccination. After infection, CD4(+) and CD8(+) T cells expand into effector cells, and then differentiate into long-lived memory cells. We show that a rare population of CD4(-)CD8(-)CD3(+)alphabeta(+)gammadelta(-)NK1.1(-) T cells has similar functions. These cells potently and specifically inhibit the growth of the intracellular bacteria Mycobacterium tuberculosis (M. tb.) or Francisella tularensis Live Vaccine Strain (LVS) in macrophages in vitro, promote survival of mice infected with these organisms in vivo, and adoptively transfer immunity to F. tularensis LVS. Furthermore, these cells expand in the spleens of mice infected with M. tb. or F. tularensis LVS, and then acquire a memory cell phenotype. Thus, CD4(-)CD8(-) T cells have a role in the control of intracellular infection and may contribute to successful vaccination.

Adoptive Transfer↗
PubMed2006

Reduced suppression or labile memory? Mechanisms of inefficient filtering of irrelevant information in older adults.

Cognitive aging theories emphasize the decrease in efficiency of inhibitory processes and attention control in normal aging, which, in turn, may result in reduction of working memory function. Accordingly, some of these age-related changes may be due to faster sensory memory decay or to inefficient filtering of irrelevant sensory information (sensory gating). Here, event-related brain potentials and the event-related optical signal were recorded in younger and older adults passively listening to tone trains. To determine whether age differentially affects decay of sensory memory templates over short intervals, trains were separated by delays of either 1 or 5 sec. To determine whether age affects the suppression of responses to unattended repeated stimuli, we evaluated the brain activity elicited by successive train stimuli. Some trains started with a shorter-duration stimulus (deviant trains). Results showed that both electrical and optical responses to tones were more persistent with repeated stimulation in older adults than in younger adults, whereas the effects of delay were similar in the two groups. A mismatch negativity (MMN) was elicited by the first stimulus in deviant trains. This MMN was larger for 1- than 5-sec delay, but did not differ across groups. These data suggest that age-related changes in sensory processing are likely due to inefficient filtering of repeated information, rather than to faster sensory memory decay. This inefficient filtering may be due to, or interact with, reduced attention control. Furthermore, it may increase the noise levels in the information processing system and thus contribute to problems with working memory and speed of processing.

Acoustic Stimulation↗
PubMed2005

Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with gammac cytokines.

The unfavorable clinical evolution in indolent non-Hodgkin lymphomas suggests defective control of neoplastic growth by the immune system. To address this issue, we evaluated phenotype, function, and maturation profile of CD4(+) and CD8(+) T cells from peripheral-blood, lymph nodes, or bone marrow of patients with B-cell non-Hodgkin lymphoma (NHL) at diagnosis. T cells from these patients frequently showed an activated but apoptosis-prone phenotype with low frequency of tumor-reactive T cells showing a TH2/Tc2 functional profile in the response to autologous tumor. In peripheral blood or in lymph nodes and bone marrow, and, in comparison to healthy donors, patients' T cells showed a skewed differentiation toward Tnaive and Tcentral memory stages, with low expression of granzyme B and perforin. T-cell culture with autologous tumor in the presence of IL-2, IL-15, and autologous bone marrow-derived cells led to massive T-cell expansion and to differentiation of cytotoxic factor(+) CD8(+) T cells releasing IFN-gamma and killing autologous B-cell tumor in an HLA-class I-restricted fashion. These results suggest impaired T-cell differentiation to effector stage in patients with B-cell NHL, but indicate that T-cell responsiveness to gammac cytokines is retained, thus allowing to promote generation of antitumor T cells for immune intervention.

Adult↗
PubMed2004

Analysis of antigen-specific B-cell memory directly ex vivo.

Helper T-cell-regulated B-cell memory develops in response to initial antigen priming as a cellular product of the germinal center (GC) reaction. On antigen recall, memory response precursors expand rapidly with exaggerated differentiation into plasma cells to produce the high-titer, high-affinity antibody(Ab) that typifies the memory B-cell response in vivo. We have devised a high-resolution flow cytometric strategy to quantify the emergence and maintenance of antigen-specific memory B cells directly ex vivo. Extended cell surface phenotype establishes a level of cellular diversity not previously appreciated for the memory B-cell compartment. Using an "exclusion transfer" strategy, we ascertain the capacity of two distinct memory B-cell populations to transfer antigen-specific memory into naive adoptive hosts. Finally, we sequence expressed messenger ribonucleic acid (mRNA) from single cells within the population to estimate the level of somatic hypermutation as the best molecular indicator of B-cell memory. In this chapter, we describe the methods used in each of these four sections that serve to provide high-resolution quantification of antigen-specific B-cell memory responses directly ex vivo.

Animals↗
PubMed1982

In vitro and in vivo allogeneic effects: differential modulation of B cell subpopulations.

We examined the sensitivity of primary TD and TI responses to allogeneic effects and found that primary TD responsive B cells were very sensitive to negative allogeneic effects elicited in vitro. The primary TI-2 responses, on the other hand, were not suppressed but rather enhanced twofold to threefold under the same culture conditions. Thus, primary B cell subsets resemble their IgG memory counterparts (1) in their differential sensitivity to allogeneic T cells. The ability of in vivo induced allogeneic effects of modulate antibody responses was studied using chronic graft-vs-host reaction (GVH) as a model. F1 mice immunized with TD (TNP-KLH, TNP-sheep-gamma-globulin) antigens shortly after GVH induction had reduced IgM and IgG primary responses. In contrast, the primary response to TNP-Ficoll was enhanced and included a large number of primary IgG PFC. Furthermore, mice undergoing chronic GVH were incapable of developing long-term memory after immunization with a TD antigen (TNP-KLH), as determined by secondary in vitro challenges with either TD or TI antigens. These mice retained helper T cells, indicating a failure of memory development in the B cell compartment. These studies suggest that the secondary TD- and TI-responding precursors (B2 gamma and B1 gamma, respectively) are probably both derived from primary B2 precursors (which are very sensitive to negative allogeneic effects). The maturation of the B1 memory population may thus be linked to increased resistance to allosuppression.

Animals↗
PubMed2002

Cytokine memory of T helper lymphocytes.

Memory is one of the key features of the adaptive immune system. Specific T and B lymphocytes are primed for a particular antigen and upon challenge with it will react faster than naive lymphocytes. They also memorize the expression of key effector molecules, in particular cytokines, which determine the type and scale of an immune reaction. While in primary activations differential expression of cytokine genes is dependent on antigen-receptor signaling and differentiation signals, in later activations the expression is triggered by antigen-receptor signaling and dependent on the cytokine memory. The molecular basis of the cytokine memory implies differential expression of transcription factors and epigenetic modifications of cytokine genes and gene loci. GATA-3 for Th2 and T-bet for Th1 cells expressing interleukin-4 or interferon-gamma, respectively, are prime candidates for key transcription factors of cytokine memory. The essential role of epigenetic modifications is suggested by the requirement of DNA synthesis for the establishment of a cytokine memory in Th lymphocytes. At present the molecular link between transcription factors and epigenetic modifications of cytokine genes in the establishment and maintenance of cytokine memory is not clear. The initial cytokine memory is not stable against adverse differentiation signals, while in repeatedly stimulated lymphocytes it is stabilized by a variety of mechanisms.

Animals↗
PubMed1990

Differences in abstraction ability with age.

Three tests of abstraction were administered to 89 optimally healthy subjects aged 30-79. Performance on all 3 tasks showed significant differences with age. This was primarily, although not entirely, the result of deficits in performance by the 70-year-old subjects. These results do not appear to be related to changes in memory ability or to a differential increase in a particular type of abstraction error.

Abstracting and Indexing↗
PubMed2003

The chemokine receptor CX3CR1 controls homing and anti-viral potencies of CD8 effector-memory T lymphocytes in HIV-infected patients.

OBJECTIVES: We have recently reported that the polymorphism of the fractalkine receptor, CX3CR1, provides a new marker for prognosis in HIV disease. In order to understand the mechanism by which CX3CR1 participates in the regulation of HIV-immune responses, we investigated its expression and role on T lymphocytes in HIV-infected patients. DESIGN: For that purpose, we analysed the expression of CX3CR1 on CD4 and CD8 effector-memory subsets in HIV-positive individuals by flow cytometric analyses, and studied its potential role in the migration and function of CD8 effector cells. RESULTS: We observed an increased frequency of CD8 cells expressing CX3CR1 that was correlated with disease progression in HIV-infected patients compared with normal individuals. CX3CR1+ was expressed mainly on activated and differentiated CCR7-CD45RA-negative memory lymphocytes. Interestingly, CX3CR1 appeared as the main homing receptor of these cells that have downmodulated most other chemokine receptors. The CD8+CX3CR1+ lymphocytes were engaged in the cytotoxic lineage (perforin+, CD27-negative and CD57+). Ex-vivo analysis showed that CX3C ligand-1 inhibits IFNgamma production in response to T cell receptor engagement. CONCLUSION: CX3CR1 and its ligand could contribute to the specific migratory pattern of late-stage differentiated CD8 cells and participate in the regulation of effector function of CD8 lymphocytes during HIV infection.

Adult↗
PubMed2000

Gestational-lactational exposure to Aroclor 1254 impairs radial-arm maze performance in male rats.

Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in children. The current study assessed effects of gestational and lactational exposure to a commercial PCB mixture, Aroclor 1254 (A1254), on spatial learning and memory in rats, using the radial-arm maze (RAM). Pregnant Long-Evans females (10/dose group) were exposed to 0 or 6-mg/kg/day A1254 (po in corn oil) from gestation day (GD) 6 to weaning at postnatal day (PND) 21. After they reached adulthood, 1 male and 1 female from each litter were tested on a working/reference memory task using a 12-arm RAM. Eight of the 12 arms were baited, with the pattern of baited arms remaining the same on every trial for each rat. Compared to control males, the A1254-exposed males made significantly more working memory errors (2.15 +/- 0.13 and 3.20 +/- 0.18 errors +/- SEM for control and A1254 males, respectively) and reference memory errors (3.17 +/- 0.10 and 4.13+/-0.14 errors +/- SEM for control and A1254 males, respectively) on the RAM. In contrast, A1254-exposed females were not impaired relative to control females on the RAM. Drug challenges with dizocilpine (MK-801) and scopolamine did not differentially affect working or reference memory of control and exposed rats. These data suggest that perinatal exposure to A1254 may cause sex-specific deficits in spatial learning and memory, and that NMDA-mediated and muscarinic neurotransmission, as assessed with the drug challenges, were not markedly impaired in the A1254-exposed animals.

Animals↗
PubMed1978

Heterogeneity of the B cell subpopulation operationally defined by (a) differentiation antigen(s) common to MOPC 104E and mature IgM plasma cells.

An antiserum raised in rabbit against MOPC 104E myeloma cells was extensively absorbed by murine IgM, thymocytes and spleen cells. Using indirect immunofluorescence, the distribution of the corresponding mouse plasma cell antigen(s) (MPCA) was determined among immunized spleen cells. Only 1-3% of the cells were stained but this MPCA-bearing subpopulation included all IgM plasma cells, a sizable proportion of IgG plasma cells and about one third of the antigen binding cells identified following deliberate immunization. It is therefore proposed that MPCA is transiently expressed during the antigen-induced differentiation of virgin B lymphocytes into memory cells as it does during the maturation process into Ig-producing cells and thus reflects the ontogenic relationship of these two differentiation pathways.

Antibody-Producing Cells↗
PubMed1992

T cell differentiation antigens on lymphocytes in the human intestinal lamina propria.

Recently, T cell subpopulations presumably representing memory T lymphocytes have been described in vitro. Intestinal lamina propria T cells (LP-T) have characteristics resembling those of memory cells. We therefore investigated the expression of surface Ag associated with memory phenotype in vitro on lamina propria lymphocytes (LPL) and PBL and on the T cell subpopulations defined by the bright expression of CD45R0 by flow cytometric analysis of isolated cell populations. LPL had significantly increased percentages of CD45R0 and CD58 positive cells compared with PBL. Whereas PBL showed bimodal expression profiles of CD45R0, CD58, and CD2, the vast majority of LPL was bright for these Ag. Expression of CD45RA was significantly reduced in both frequency and intensity in LPL, and LPL had significantly reduced percentages of CD11a/CD18 and CD29 positive cells compared with PBL. The CD45R0 bright T cell subpopulations of both PBL and LPL were characterized by a lack of CD45RA. CD45R0 bright T cells from the peripheral blood (PB-T) were predominantly bright for CD2, CD58, CD29, and CD11a/CD18 whereas CD45R0 dim PB-T had bimodal expression profiles and CD45R0 negative PB-T were dim or even negative for these Ag. CD45R0 bright LP-T were also bright for CD2 and CD58 but had significantly reduced surface densities of CD11a/CD18 and CD29 compared with CD45R0 bright PB-T. The surface density of CD29 on CD45R0 bright LP-T corresponded to that of CD45R0 negative PB-T, and a significant proportion of CD45R0 bright LP-T was even negative for CD11a/CD18 and CD29. Additionally, CD45R0 bright LP-T in contrast to PB-T were characterized by a lack of 1-selectin and the expression of CDw49a and the mucosa-specific T cell Ag HML-1 on high percentages of cells. Our results show that the phenotype of CD45R0 bright T cells from the lamina propria clearly deviates from that of memory T cells in vitro and of CD45R0 bright T cells in the peripheral blood. We conclude that memory T cell populations in vivo undergo specific differentiation depending on their tissue localization, leading to unique phenotypic and presumably functional features.

Adult↗
PubMed2006

Th1 memory: implications for vaccine development.

T-helper 1 (Th1) cells play a critical role, via interferon-gamma (IFN-gamma) production, in mediating intracellular killing against a variety of infectious pathogens. Thus, understanding the regulation of Th1 responses could provide better insight into vaccine design for infections requiring Th1 immunity. The cellular and molecular mechanisms that control the induction of Th1 effector cells have been well characterized. More recently, there has been substantial progress in furthering our understanding of the factors that regulate the development of Th1 memory cells. It is clear that Th1 responses are functionally heterogeneous, as defined by their ability to produce IFN-gamma. Furthermore, this heterogeneity has profound implications for the capacity of distinct lineages of Th1 cells to develop into memory cells. This review emphasizes the mechanisms controlling the differentiation of naïve CD4+ T cells into effector and then memory cells in a progressive manner. It highlights the importance of IFN-gamma as a positive regulator for inducing Th1 responses but a negative regulator for sustaining Th1 effector cells. In conclusion, we discuss how this current understanding of Th1 differentiation will inform vaccine design and better define immune correlates of protection.

Animals↗