Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “memory differentiation”

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.

At least 379 records · Page 21Linked to original sources
PubMed2003

Cytokine-driven proliferation and differentiation of human naïve, central memory and effector memory CD4+ T cells.

Memory T lymphocytes divide in vivo in the absence of antigen maintaining a pool of central memory (T(CM)) and effector memory cells (T(EM)) with distinct effector function and homing capacity. We compared human CD4+ naïve T, T(CM) and T(EM) cells for their capacity to proliferate in response to cytokines, which have been implicated in T cell homeostasis. Interleukin (IL)-7 and IL-15 expanded with very high efficiency T(EM), while T(CM) were less responsive and naïve T cells did not respond at all. Dendritic cell (DC)-derived cytokines allowed naïve T cells to respond selectively to IL-4 and potently boosted the response of T(CM) to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rss and the common gamma chain (gamma(c)). The ERK and the p38 MAP kinases were selectively required for TCR and cytokine-driven proliferation, respectively. Importantly, in cytokine-driven cultures T(CM) proliferated and some of the proliferating cells acquired effector function and non-lymphoid tissue homing capacity. Ex vivo BrdU incorporation experiments showed that both T(CM) and T(EM) proliferated under steady state conditions in vivo. Altogether these results provide a plausible mechanism for the maintenance of a polyclonal and functionally diverse repertoire of human CD4+ memory T cells and for a sustained antigen-independent generation of T(EM) from a pool of T(CM) cells.

Animals↗
PubMedDate not supplied

In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze.

Male and female mice and rats were tested on a water escape version of the radial-arm maze designed to measure working and reference memory. In both species, females exhibited superior working memory during acquisition, and were better able to handle a higher memory load. However, male mice and rats exhibited better reference memory than females during the asymptotic portion of testing. Our data suggest that females may be better at working memory when both working and reference memory information must be learned simultaneously, and males better at reference memory when it has been differentiated from working memory.

Animals↗
PubMed1998

Aging and ischemia in gerbils impair spatial memory performance.

Gerbils aged 3 months and 24+ months were subjected to 5 min of global forebrain ischemia and tested in a radial arm maze (1 trial/day, 50 days). Compared with age-matched, sham-operated controls, ischemic animals were impaired on measures of both working and reference memory. Aged animals were impaired on working memory, but not on reference memory, compared with their younger counterparts. Hippocampal CA1 and CA2 regions were significantly and comparably damaged in the 2 ischemic groups but were unaffected by aging. The results suggest that aging and ischemia have functionally similar effects on working memory, but the 2 processes differentially impact reference memory.

Age Factors↗
PubMed2006

In vitro generated human memory-like T cells are CD95 type II cells and resistant towards CD95-mediated apoptosis.

An adaptive immune response implies expansion of activated T cells and subsequent elimination to maintain homeostasis in a process called activation-induced cell death. Some cells, however, differentiate into memory cells and ensure a strong secondary immune response. To analyze the apoptosis phenotype of memory T cells on a cellular and molecular level, we have established an in vitro model of T cell activation and generation of cells phenotypically and functionally similar to memory cells. These long-term cultured T cells show a CD95-resistant phenotype, although they are still sensitive towards TCR/CD3-mediated apoptosis. Biochemical analysis revealed that these cells shift from CD95 type I (direct signaling from the receptor) during the effector phase to CD95 type II cells (dependent on the mitochondrial amplification loop). Moreover, their mitochondria are protected, probably due to high expression levels of Bcl-x(L) and Bcl-2. Thus, our data suggest a mechanism how memory T cells acquire resistance towards bystander cell death via the CD95 system.

Apoptosis↗
PubMed2005

"Where to?" remote memory for spatial relations and landmark identity in former taxi drivers with Alzheimer's disease and encephalitis.

Recent research suggests that the hippocampus is not needed for the maintenance and recovery of extensively used environments learned long ago. Instead, a network of neocortical regions differentially supports memory for locationnavigation knowledge and visual appearance of well-known places. In this study, we present a patient, S. B., who was diagnosed with probable Alzheimer's disease long after retiring from his 40 years as a taxi driver in downtown Toronto, a place that he has visited rarely, if ever, in the last decade. His performance was compared to that of two other retired taxi drivers, L. R., who developed encephalitis after retirement, and I. L., who is without neurological illness, and a group of eight healthy control participants who were never taxi drivers but all of whom worked or lived in downtown Toronto until at least 10 years ago. Despite S. B.'s widespread atrophy, which has affected mainly his hippocampus and part of his occipitotemporal cortex, he performed at least as well as all other participants on remote memory tests of spatial location and mental navigation between well-known Toronto landmarks. Unlike the comparison populations, however, he was unable to discriminate between the appearances of landmarks that he had visited frequently in his many years as a taxi driver from unknown buildings. This profound deficit extended to famous world landmarks but not to famous faces and does not appear to be semantic in nature. These findings add further support to the claim that the hippocampus is not necessary for mental navigation of old environments and suggest that expertise is not sufficient to protect against landmark agnosia.

Aged↗
PubMed2002

In vivo activation of melanoma-specific CD8(+) T cells by endogenous tumor antigen and peptide vaccines. A comparison to virus-specific T cells.

Many new types of vaccines against infectious or malignant diseases are currently being proposed. Careful characterization of the induced immune response is required in assessing their efficiency. While in most studies human tumor antigen-specific T cells are analyzed after in vitro re-stimulation, we investigated these T cells directly ex vivo using fluorescent tetramers. In peripheral blood lymphocytes from untreated melanoma patients with advanced disease, a fraction of tumor antigen (Melan-A/MART-1)-specific T cells were non-naive, thus revealing tumor-driven immune activation. After immunotherapy with synthetic peptides plus adjuvant, we detected tumor antigen-specific T cells that proliferated and differentiated to memory cells in vivo in some melanoma patients. However, these cells did not present the features of effector cells as found in cytomegalovirus specific T cells analyzed in parallel. Thus, peptide plus adjuvant vaccines can lead to activation and expansion of antigen specific CD8(+) T cells in PBL. Differentiation to protective CD8(+) effector cells may, however, require additional vaccine components that stimulate T cells more efficiently, a major challenge for the development of future immunotherapy.

Adjuvants, Immunologic↗
PubMed2001

Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells.

Memory T lymphocytes proliferate in vivo in the absence of antigen maintaining a pool of central memory T cells (T(CM)) and effector memory T cells (T(EM)) with distinct effector function and homing capacity. We compared human CD4(+) naive T, T(CM), and T(EM) cells for their capacity to proliferate in response to cytokines, that have been implicated in T cell homeostasis. Interleukin (IL)-7 and IL-15 expanded with very high efficiency T(EM), while T(CM) were less responsive and naive T cells failed to respond. Dendritic cells (DCs) and DC-derived cytokines allowed naive T cells to proliferate selectively in response to IL-4, and potently boosted the response of T(CM) to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rbeta and the common gamma chain (gamma(c)). The extracellular signal regulated kinase and the p38 mitogen-activated protein (MAP) kinases were selectively required for TCR and cytokine-driven proliferation, respectively. Importantly, in cytokine-driven cultures, some of the proliferating T(CM) differentiated to T(EM)-like cells acquiring effector function and switching chemokine receptor expression from CCR7 to CCR5. The sustained antigen-independent generation of T(EM) from a pool of T(CM) cells provides a plausible mechanism for the maintenance of a polyclonal and functionally diverse repertoire of human CD4(+) memory T cells.

CD4-Positive T-Lymphocytes↗
PubMed2006

The fate of effector CD8 T cells in vivo is controlled by the duration of antigen stimulation.

What controls the fate of the T-cell response remains incompletely defined. Gain of effector function facilitated by costimulation has been thought to be a crucial factor in determining the outcome of the T-cell response, i.e. long-term memory in the presence of costimulation versus tolerance induction in the absence of costimulation. In this study, we show that while costimulation or cognate CD4 helps to promote the acquisition of effector function during the initial phase of the CD8 T-cell response, the fate of effector CD8 T cells is controlled by the duration of subsequent antigenic stimulation. Effector CD8 T cells differentiate into memory cells only after clearance of antigen, whereas in the presence of persistent antigen, effector CD8 T cells are tolerized. Furthermore, protective immunity against tumour cannot develop in the persisting antigen environment. These results suggest that removal of persisting antigen by other means might be a prerequisite for effective immunotherapy in cancer.

Adoptive Transfer↗
PubMed1998

Facilitatory effects of chronically administered citicoline on learning and memory processes in the dog.

1. Citicoline (cytidine (5') diphosphocholine) has been shown to reverse aging-induced memory deficits, scopolamine-induced amnesia and nucleus basalis magnocellularis lesion-induced learning impairment. 2. This study aimed to evaluate the effects of citicoline on learning and retrieval processes in a complex differential reinforcement of response duration schedule in normal dogs. 3. The effects of citicoline on a stabilized performance were also measured in order to be able to differentiate specific memory effects from non specific influences on the motor, neuro-vegetative and motivational systems. 4. The results demonstrate that citicoline can exert facilitatory effects on learning and memory but also on retrieval processes. The complete absence of effects on the stabilized performance and on the motor, neuro-vegetative and motivational systems constitutes arguments in favour of a selectivity of action on the memory processes.

Acoustic Stimulation↗
PubMed2001

New questions on the hemispheric encoding/retrieval asymmetry (HERA) model assessed by divided visual-field tachistoscopy in normal subjects.

According to the hemispheric encoding/retrieval asymmetry (HERA) model, based on data obtained through functional neuroimaging, the left and right prefrontal cortices are preferentially, and, respectively, involved in long-term episodic memory encoding and retrieval. In this study, the HERA model was tested from a behavioral perspective using divided visual-field tachistoscopy. A recognition paradigm with both verbal and visuospatial materials was devised to differentiate memory-related effects (encoding vs. retrieval) from effects linked to the materials. The paradigm used lists of 12 and four items to assess long-term episodic memory and short-term memory, respectively. The aim of the latter condition was to test whether the HERA model is applicable in short-term memory. For long-term episodic memory, the data obtained validated the HERA model; the direction of the hemispheric asymmetry was found to depend on the type of materials used, whereas its magnitude was determined by the type of memory process. For verbal short-term memory, the HERA model seems to be confirmed. The pre-existing representations of the material could take into account the similarity of the hemispheric asymmetry pattern between short-term memory and long-term memory. In contrast, for visuospatial short-term memory, Baddeley's working memory model seems to better explain our results insofar as the asymmetries were essentially linked to the material in encoding but not in retrieval. This latter difference between short-term memory and long-term indicates that processes involved in LTM depend on episodic processes per se, hence, lending more support for the HERA model. Accordingly, these two memory systems seem to bring into play two different modes of hemisphere specialization.

Adult↗
PubMed1990

Myelomas and lymphomas expressing the Ig gamma 2a H chain gene have similar transcription termination regions.

During B cell differentiation, the membrane and secretion specific forms of the Ig gamma-H chains of mouse are differentially expressed as a function of the developmental stage of the cell. Representatives of less differentiated and memory B cells (lymphomas) that have undergone the class switch to gamma 2a or gamma 2b H chains produce nearly equal amounts of membrane specific (gamma m) vs secretory specific (gamma s) mRNA. Fully differentiated gamma 2a or gamma 2b plasma cells and their tumors, myelomas, switch to higher levels of gamma s mRNA production relative to gamma m. Selective use of either the gamma s poly(A) site or the downstream gamma m poly(A) site accompanied by specific splicing events could modulate production of these two forms of mature gamma H chain mRNA. Alternatively, transcription termination could be modulated. Through a combination of hybrid protection and in vitro nascent RNA analyses of transcripts from gamma H chain-producing cells arrested at various stages of development, we have mapped transcription termination in both lymphomas (gamma s approximately gamma m mRNA) and in myelomas (gamma s much greater than gamma m) mRNA. Regardless of the developmental stage of the cell, transcription proceeds at a significant level through both the secretory- and membrane-specific poly(A) sites and terminates at least 500 nucleotides downstream of the gamma m poly(A) site in both the gamma 2a and gamma 2b genes. We conclude that transcription termination does not play a major role in the switch to elevated levels of gamma s production in late stage gamma-producing myeloma cells and that alternative RNA processing alone must be responsible for the differential expression of the gamma H chain mRNA.

Animals↗
PubMed1991

Expression of CD31 epitopes on human lymphocytes: CD31 monoclonal antibodies differentiate between naive (CD45RA+) and memory (CD45RA-) CD4-positive T cells.

The CD31 antigen, a member of the immunoglobulin superfamily with a possible cell adhesion function, is expressed on approximately 50% of peripheral blood lymphoid cells at relatively low intensity (10-20% of the level on monocytes). In the accompanying paper we showed that a mAb, 5A2.G5, which identifies a glycosylation-dependent epitope of the CD31 antigen, bound to fewer lymphocytes than two other CD31 mAb, B2B1 and 2BD4, although the 3 antibodies bound equally well to monocytes. We have now analyzed the pattern of expression of epitopes of the CD31 antigen on lymphoid cell subpopulations using two-color immunofluorescence and flow cytometry. Large granular lymphocytes (CD16+), CD8-positive T cells and B cells (SMIg+) were mostly CD31-positive as indicated by the binding of mAb B2B1 and 2BD4. Single populations displaying some overlap with the negative control were obtained in each case. In contrast, CD4-positive T cells fell into two discrete populations with respect to CD31 antigen expression. mAb 5A2.G5 displayed weaker binding to all lymphoid cell types, indicating that the pattern of glycosylation of the CD31 antigen differs between lymphocytes (of all types) and cells of the myeloid lineages. The heterogeneity of CD31 antigen expression by CD4-positive cells was further examined by dual-labelling of purified CD4 cells with mAb B2B1 and CD45RA or CD29 mAb which identify naive and memory T cells respectively. The CD31 antigen was found to be preferentially expressed by the CD45RA-positive, naive cell population.

Antibodies, Monoclonal↗
PubMed1991

Peyer's patch B cells with memory cell characteristics undergo terminal differentiation within 24 hours in response to interleukin-6.

Culture of Peyer's patch (PP) B cells with interleukin-6 (IL-6) for 7 days results in a six- to eightfold increase in secretion of IgA, while little or no increase in IgM or IgG secretion occurs in these cultures. Further, greater than 80% of IgA is produced within the first 72 h of culture. Using a sensitive enzyme-linked immunospot (ELISPOT) assay, we have shown that culture of PP B cells with IL-6 for 24 h gave increased IgA spot-forming cells (SFC) (4- to 6- fold) even though secreted IgA, as measured by RIA, had only increased 1.6- to 2.0-fold. In addition, significant increases in IgA SFC numbers could be demonstrated as early as 4 h after addition of IL-6. The increase in IgA secretion was not the result of IL-6-induced B-cell proliferation, since culture of B cells with IL-6 resulted in no increase in [3H]thymidine incorporation compared to untreated controls. This was supported by studies with mitomycin C which, when added to B cell cultures, had no effect on the IL-6-induced increase in numbers of IgA SFC. Increased IgA secretion was totally abolished by actinomycin D, an inhibitor of RNA transcription, showing that continued production of alpha mRNA is essential for IL-6-induced IgA secretion. Separation of PP B cells into peanut agglutin (PNA)Hi (germinal center [GC]) and PNALo (non-GC) subpopulations before culture with IL-6 showed that only PNALo B cells transcribe increased levels of alpha mRNA message and secrete high levels of IgA in response to this cytokine. Although the GC are the site of B-cell proliferation and presumably of switching to IgA and contain 70 to 85% of sIgA+ B cells in the PP, these PNAHi B cells do not respond to IL-6. This suggests that memory sIgA+ B cells in PP express IL-6 receptor (IL-6R) and respond to this cytokine with rapid differentiation into plasma cells that secrete IgA.

Animals↗
PubMedDate not supplied

Appearance of human plasma cells following differentiation of human B cells in NOD/SCID mouse spleen.

Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies. To address this issue, we transplanted human peripheral blood mononuclear cells (PBMC) directly into the spleen of irradiated NOD/SCID mice depleted of natural killer cell activity. Within 6 weeks, naive B cells differentiated into memory B cells and, importantly, the numbers of human CD138+ plasma cells in spleen increased by 100 fold after transplantation. Plasma cell numbers correlated with the detection of human IgM and IgG in serum, indicating that human B cells had differentiated into mature plasma cells in the murine spleen. In addition to CD19+ plasma cells, a distinct CD19- plasma cell population was detected, suggesting that downregulation of CD19 associated with maturation of plasma cells occurred. When purified human B cells were transplanted, those findings were not observed. Our results indicate that differentiation and maturation of human B cells and plasma cells can be investigated by transplantation of human PBMC into the spleen of NOD/SCID mice. The model will be useful for studying the differentiation of human B cells and generation of plasma cells.

Animals↗
PubMedDate not supplied

Adhesion molecules in HIV-related and idiopathic polymyositis: immunohistochemical studies.

Idiopathic polymyositis (IPM) and HIV polymyositis (HIV-PM) are considered to be related autoimmune diseases whose target is skeletal muscle. They have been associated to a T cell-mediated and MHC-I-restricted cytotoxic phenomenon, but both etiology and physiopathology remain incompletely understood. Their histological hallmarks are mononuclear leukocyte infiltrates as well as necrosis, degeneration, and regeneration of muscle fibers. In the present study, we have investigated the immunohistochemical expression of cell adhesion molecules, cytokines, and leukocyte surface antigens in biopsies of HIV-PM and IPM patients. The aim was to better define factors involved in lymphocyte recruitment and in inflammatory changes seen in PM. Notable upregulation of ICAM-1 and TNF-alpha was detected on capillary and venular endothelia and on inflammatory cells, whereas no significant VCAM-1 and ELAM-1 expression was present. LFA-1, the main ICAM-1 counter-receptor, was found to be highly expressed on lymphocytes and monocytes, especially at the vicinity of damaged fibers. The majority of infiltrating cells were CD8+CD45 RO-T cells, which are thought to have memory capacities. These findings suggest that in IPM and HIV-PM, enhanced ICAM-1 and LFA-1 expression possibly induced by TNF-alpha, may regulate the homing process of selected lymphocyte clones in muscle tissue. Lymphocyte proliferation and differentiation into memory subsets may further potentiate tissue-restricted homing capabilities.

Adult↗
PubMed2005

TuJ1 (class III beta-tubulin) expression suggests dynamic redistribution of follicular dendritic cells in lymphoid tissue.

Follicular dendritic cells (FDCs) play central roles in the B cell survival, proliferation, and differentiation into memory cells. Here, we show that TuJ1 (class III beta-tubulin) is expressed strongly in FDCs of human lymphoid tissue. TuJ1 has been a marker of neurons in the central and peripheral nervous systems from the early stage of neural differentiation. FDCs expressed TuJ1 protein diffusely in both light and dark zones of germinal centers in all human lymphoid tissues. In contrast, CD21 expression was relatively concentrated to the light zone, suggesting that TuJ1 was a marker for FDCs with broader spectrum than CD21. In addition to the germinal center, there were single TuJ1-expressing cells scattered in the mantle zone, blurring the border of the FDC network. In human tonsils, single scattered TuJ1-positive cells were also present in the crypt epithelium, suggesting a dynamic redistribution of FDCs among the antigen-rich epithelium, mantle zone, and germinal center. Such migration of FDCs could reflect a way of direct transport of various antigens carried on their surface to the germinal center, and a basis for the polarity of lymphoid follicles toward the epithelium in mucosa-associated lymphoid tissues. HK cells, cultured FDCs, also expressed TuJ1. The expression of TuJ1 by FDCs suggests that they may share certain biological characteristics of the neural system.

Blotting, Western↗
PubMed2026

TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro.

T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells play critical roles in regulating the activity of the germinal center (GC), which is essential for the generation of high-affinity antibodies. In the GC, Tfh cells help B cells to proliferate and to differentiate into memory B cells and long-lived plasma cells. In contrast, Tfr cells, a specialized subset of regulatory T cells (Tregs), modulate the humoral immune response by suppressing excessive or autoreactive B-cell activity. Here, we established an in vitro differentiation protocol for mouse CD4⁺ T cells that yielded CXCR5⁺FoxP3⁺ Tfr cells that exhibited a Bcl6hiPD-1hiCD25loGITRint phenotype and were distinct from Treg and Tfh cells. Functionally, in vitro-generated Tfr cells potently suppressed Tfh cell-driven B-cell class switching to IgG1 and downregulated the expression of B-cell costimulatory ligands. While in vitro-generated Bcl6-deficient Tfh cells were impaired in providing help to B cells for efficient class switching to IgG1, in vitro-generated Bcl6-deficient Tfr cells failed to inhibit Tfh cell-driven B-cell class switching to IgG1. Mechanistically, we showed that Tfr cells emerged from FoxP3+ precursors in low-IL-2 environments through a TGF-β- and c-Maf-dependent pathway, allowing for reprogramming and reinforcement of the follicular regulatory cell program in CD4+ T cells in vitro.

Animals↗
PubMed1983

Effects of cholera toxin on the lymphoid system. III. In vivo generation of cytotoxic lymphocytes.

Cytotoxic T lymphocytes (CTL) were generated in the spleen by subcutaneous inoculation of EL-4 leukaemia cells (H-2b) into C3H/He mice (H-2k). (1) Cytotoxicity of spleen cells was profoundly suppressed by an intravenous injection of 1 microgram cholera toxin on the day of tumor inoculation. Tumors continued to grow progressively. (2) Differentiation of memory cells to mature CTL was suppressed by cholera toxin injection on the day of booster inoculation of EL-4 cells. The tumors grew progressively in immune mice given cholera toxin on the day of the booster. (3) In vitro treatment of CTL with cholera toxin suppressed the expression of their cytotoxic activity to a considerable extent. However, tumors regressed very rapidly after rechallenge to immune mice carrying CTL, even when cholera toxin was injected on the day of rechallenge. Cholera toxin suppressed not only the functional expression of CTL but also the induction phase of CTL generation.

Animals↗