Search results for "phenomena"
showing 10 items of 8379 documents
The molecular basis of cancer immunotherapy by cytotoxic T lymphocytes.
1998
The disappointing clinical results of cancer immunotherapy of the past few decades have not diminished the optimism about the potential of the new generation of immunotherapeutic strategies towards treatment of malignant disease. Tremendous progress has been made over recent years in unveiling the molecular basis of antigen presentation and recognition by cytotoxic T lymphocytes (CTL). The molecular concepts that have emerged from these studies have led to the design of novel anticancer vaccines and CTL-based immunotherapeutics. This review is to highlight the current molecular insights of antigen presentation and CTL recognition/activation, and their impact on the rational design of therap…
The Role of the Amygdala in the Extinction of Conditioned Fear
2006
The amygdala has long been known to play a central role in the acquisition and expression of fear. More recently, convergent evidence has implicated the amygdala in the extinction of fear as well. In rodents, some of this evidence comes from the infusion of drugs directly into the amygdala and, in particular, into the basolateral complex of the amygdala, during or after extinction learning. In vivo electrophysiology has identified cellular correlates of extinction learning and memory in the lateral nucleus of that structure. Human imaging experiments also indicate that amygdaloid activity correlates with extinction training. In addition, some studies have directly identified changes in mole…
Enhancing memory performance with rTMS in healthy subjects and individuals with Mild Cognitive Impairment: the role of the right dorsolateral prefron…
2012
A debated question in the literature is the degree of anatomical and functional lateralization of the executive control processes subserved by the dorsolateral prefrontal cortex (DLPFC) during recognition memory retrieval. We investigated if transient inhibition and excitation of the left and right DLPFC at retrieval by means of repetitive transcranial magnetic stimulation (rTMS) modulate recognition memory performance in 100 healthy controls (HCs) and in 8 patients with Mild Cognitive Impairment (MCI). Recognition memory tasks of faces, buildings and words were used in different experiments. rTMS-inhibition of the right DLPFC enhanced recognition memory of verbal and non verbal material in…
Dendritic Cell-Specific Biolistic Transfection Using the Fascin Gene Promoter
2012
The transcriptional targeting of gene expression to selected cells by cell type-specific promoters displays a fundamental tool in gene therapy. In immunotherapy, dendritic cells (DCs) are pivotal for the elicitation of antigen-specific immune responses following gene gun-mediated biolistic transfection. Here we report on transcriptional targeting of murine skin DCs using plasmids which include the promoter of the gene of the cytoskeletal protein fascin to control antigen production. Fascin, which is mandatory for the formation of dendrites, is synthesized among the hematopoietic cells exclusively by activated DCs. The activity of the promoter of the fascin gene reflects the endogenous produ…
Host-Derived CD8+ Dendritic Cells Protect Against Acute Graft-versus-Host Disease after Experimental Allogeneic Bone Marrow Transplantation
2014
Graft-versus-host disease (GVHD) is a frequent life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT) and induced by donor-derived T cells that become activated by host antigen-presenting cells. To address the relevance of host dendritic cell (DC) populations in this disease, we used mouse strains deficient in CD11c(+) or CD8α(+) DC populations in a model of acute GVHD where bone marrow and T cells from BALB/c donors were transplanted into C57BL/6 hosts. Surprisingly, a strong increase in GVHD-related mortality was observed in the absence of CD11c(+) cells. Likewise, Batf3-deficient (Batf3(-/-)) mice that lack CD8α(+) DCs also displayed a strongly incr…
Peripherally Circulating CD4+ FOXP3+ CXCR3+ T Regulatory Cells Correlate with Renal Allograft Function
2012
Peripheral immunoregulation depends on T regulatory cell trafficking into the allograft to modulate the local alloresponse. Little is known about the relevance of trafficking receptors for Tregs after solid organ transplantation in humans. In this study, expression of the peripheral chemokine receptors CXCR3 and CCR5 on CD4+ FOXP3+ Treg cells was analysed and correlated with allograft function in renal transplant recipients. Flow cytometry analysis of peripheral blood mononuclear cells of 54 renal transplant recipients receiving a calcineurin inhibitor-based immunosuppression was performed for CD4, CD25, FOXP3, CXCR3 and CCR5 within the first 18 months post-transplantation. Correlation anal…
IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1
2007
IL-27 is an IL-12-related cytokine frequently present at sites of inflammation that can promote both anti- and pro-inflammatory immune responses. Here, we have analyzed the mechanisms how IL-27 may drive such divergent immune responses. While IL-27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti-inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL-27 suppressed the development of adaptive, TGF-beta-induced Forkhead box transcription factor p3-positive (Foxp3(+)) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg develo…
Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer
2001
We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the widely expressed human MDM2 oncoprotein and were able to bypass self-tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic mice and by generating A2.1-negative, allo-A2.1-restricted human T lymphocytes. A broad range of malignant, as opposed to nontransformed cells, were killed by high-avidity transgenic mouse and allogeneic human CTLs specific for the A2.1-presented MDM2 epitope. Whereas the self-A2.1-restricted human T cell repertoire gave rise only to low-avidity CTLs unable to recognize the natural MDM2 peptide, human A2.1+ T lymphocytes were turned into efficient MDM2-specific CTLs upon exp…
An unconventional TRAIL to cancer therapy
2013
Cellular immunotherapy offers novel, safe, and effective routes to treating cancer. However, approaches utilizing cytotoxic CD8+ T cells are hampered by the need to identify suitable target antigens that are expressed by tumor cells but not healthy tissues, and that are recognized with sufficient affinity. Most importantly, the applicability of CD8+ T-cell-based therapies is governed by the MHC restriction of tumor-specific epitopes, thereby limiting the potential benefit to patients carrying the appropriate MHC haplotype. Alternative approaches to harness the immune system against tumors exploit non-MHC-restricted γδ T cells that recognize stress-induced changes in transformed cells. A new…
Major histocompatibility complex regulation of cytokine production.
1996
This review describes the phenomenon of the major histocompatibility complex (MHC) control of cytokine production both in experimental animals and in humans. H-2 (mouse MHC) regulates which type of cytokine is selectively produced in response to the hapten trinitrophenyl (TNP). T cells from TNP-immune H-2k mice produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-3, IL-5, tumor necrosis factor-alpha (TNF-alpha), IL-10, and very low levels of IL-4 on reexposure to the specific antigen in vitro. By contrast, T cells from H-2d mice produce IL-3, TNF-alpha, IL-10, and IL-4 but very low levels of IL-2, IL-5 and IFN-gamma. As MHC-congenic matched strains (BALB/k and BALB/c) are used, th…