The Infona portal uses cookies, i.e. strings of text saved by a browser on the user's device. The portal can access those files and use them to remember the user's data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser.
The immune evasion protein US3 of human cytomegalovirus binds to and arrests MHC class I molecules in the endoplasmic reticulum (ER). However, substantial amounts of class I molecules still escape US3-mediated ER retention, suggesting that not all class I alleles are affected equally by US3. Here, we identify tapasin inhibition as the mechanism of MHC retention by US3. US3 directly binds tapasin and...
Regulatory T cells play an important role in the maintenance of immunological self-tolerance by suppressing immune responses against autoimmune diseases and cancer. Little is known, however, about the nature of the physiological target antigens for CD4 + regulatory T (Treg) cells. Here we report the identification of the LAGE1 protein as a ligand for tumor-specific CD4 + Treg cell...
Virus-specific memory T cell populations demonstrate plasticity in antigenic and functional phenotype, in recognition of antigen, and in their ability to accommodate new memory T cell populations. The adaptability of complex antigen-specific T cell repertoires allows the host to respond to a diverse array of pathogens and accommodate memory pools to many pathogens in a finite immune system. This is...
Microbial heat shock proteins (HSPs) have been implicated in the induction of both the innate and adaptive arms of the immune response. We now show that human dendritic cells (DC) pulsed with peptide-loaded mycobacterial HSP70 complexes generate potent antigen-specific cytotoxic lymphocyte (CTL) responses, which are dependent on an HSP70-stimulated calcium signaling cascade. From the calculated peptide...
A recent workshop on ''Dendritic Cells: Biology and Therapeutic Applications,'' sponsored by the Juan March Foundation, brought together basic and clinical research scientists to discuss the mechanisms underlying the control of immune responses and tolerance by dendritic cells (DCs), as well as recent research in cancer immunotherapy based on DC vaccination. Particular emphasis was placed on antigen...
The physiological benefit of the febrile response is poorly understood. Here we show that fever-range thermal stress enhances the function of the L-selectin lymphocyte homing receptor through an interleukin-6 (IL-6)-dependent signaling mechanism. Thermal stimulation of L-selectin adhesion in vitro and in vivo is mediated by engagement of the gp130 signal-transducing chain by IL-6 and a soluble form...
By combining cell surface staining with fluorochrome-conjugated monoclonal antibodies and Hoechst 33342 dye supravital staining, Matsuzaki et al. have succeeded in enriching hematopoietic stem cells (HSCs) essentially to homogeneity. When single-cell transplantation analysis was performed using the isolated cells, over 95% of the recipient mice showed long-term multilineage engraftment. The work demonstrates...
Single-cell transplantation analysis revealed that the cells that had the strongest dye efflux activity (''Tip''-SP cells) and had the phenotype CD34- c-Kit+ Sca-1+ Lin- (CD34- KSL cells) exhibited very strong proliferation and multilineage differentiation capacity. Ninety-six percent of the lethally irradiated mice that received a single ''Tip''-SP CD34- KSL cell showed significant donor cell engraftment...
T cells play a central role in the recognition and elimination of foreign pathogens. Signals through the T cell receptor (TCR) control the extent and duration of the T cell response. To ensure that T cells are not inappropriately activated, signaling pathways downstream of the TCR are subject to multiple levels of positive and negative regulation. Herein, we describe two related proteins, Sts-1 and...
The molecular consequence of the fever response has been illuminated by a recent study showing that a temperature shift to 40 o C resulted in increased leukocyte adhesion to tissue sections, which was mediated by L-selectin activation in lymphocytes. This L-selectin activation during heat responses was dependent on IL-6 trans-signaling via the soluble IL-6R.
A potential shortcoming of nonlive vaccines is their relative inefficiency in generating T cell responses, thus limiting their application in infections requiring cellular immunity. Here, we present a system to induce cellular immunity and to study the immunological implications of time-delayed dendritic cell (DC) apoptosis and antigen reprocessing in vivo. We generated a self-replicating cytopathic...
Chemokines regulate rapid leukocyte adhesion by triggering a complex modality of integrin activation. We show that the small GTPase RhoA and the atypical ζ PKC differently control lymphocyte LFA-1 high-affinity state and rapid lateral mobility induced by chemokines. Activation of LFA-1 high-affinity state and lateral mobility is controlled by RhoA through the activity of distinct effector regions,...
Differential Ly6C expression identifies a major phenotypic division in CD44 lo CD62L hi CD4 + Th cells. Using two separate models of single subset adoptive transfer, we demonstrate the unique capacity of Ly6C hi Th cells to promote antigen-specific plasma cell production in vivo. In contrast, both compartments support germinal center formation and proliferate...
The alloimmune response can be divided into specific junctures where critical decisions between tolerance and immunity are made which define the outcome of the transplant. At these ''decision nodes'' various cytokines direct alloresponsive T cells to develop either a proinflammatory response aimed at graft destruction or an immunoregulatory response facilitating graft acceptance. This review will...
A common feature of many infections is that many pathogen-specific memory T cells become established in diverse nonlymphoid tissues. A mechanism that promotes the retention and survival of the memory T cells in diverse tissues has not been described. Our studies show that the collagen binding α1β1 integrin, VLA-1, is expressed by the majority of influenza-specific CD8 T cells recovered from nonlymphoid...
To determine the importance of suppressor of cytokine signaling-3 (SOCS3) in the regulation of hematopoietic growth factor signaling generally, and of G-CSF-induced cellular responses specifically, we created mice in which the Socs3 gene was deleted in all hematopoietic cells. Although normal until young adulthood, these mice then developed neutrophilia and a spectrum of inflammatory pathologies....
IL-4 secreting and nonsecreting cells from Th2 cultures have a similar probability of producing IL-4 upon subsequent stimulation, implying that there is stochastic element in IL-4 production by stimulated Th2 cells. Purified IL-4 producers and nonproducers have similar Gata3 and c-maf mRNA expression. Il4 gene accessibility, analyzed by restriction enzyme accessibility (REA) at sites in the promoter,...
The involvement of microphthalmia transcription factor (MITF) in the function of mast cells, melanocytes, and osteoclasts has recently started to be investigated in depth. In a previous study, we found Hint to be associated with MITF in mast cells and showed that it suppresses MITF's transcriptional activity. Here, we have found that lysyl-tRNA synthetase (LysRS) is also associated with MITF and forms...
To establish whether the widely expressed regulator of Src family kinases Csk contributes to the control of acute inflammation in vivo, we inactivated csk in granulocytes by conditional mutagenesis (Cre/loxP). Mutant mice (Csk-GEcre) developed acute multifocal inflammation in skin and lung. Animals were protected from the disease in a microbiologically controlled environment, but remained hypersensitive...
Multiple myeloma (MM) remains largely incurable despite conventional and high-dose therapies. Therefore, novel biologically based treatment approaches are urgently required. Here we demonstrate that expression of peroxisome proliferator-activated receptor γ (PPARγ) in MM cells and its agonists 15-d-PGJ2 and troglitazone completely abolished IL-6-inducible MM cell proliferation and induced apoptosis...
Set the date range to filter the displayed results. You can set a starting date, ending date or both. You can enter the dates manually or choose them from the calendar.