Serwis Infona wykorzystuje pliki cookies (ciasteczka). Są to wartości tekstowe, zapamiętywane przez przeglądarkę na urządzeniu użytkownika. Nasz serwis ma dostęp do tych wartości oraz wykorzystuje je do zapamiętania danych dotyczących użytkownika, takich jak np. ustawienia (typu widok ekranu, wybór języka interfejsu), zapamiętanie zalogowania. Korzystanie z serwisu Infona oznacza zgodę na zapis informacji i ich wykorzystanie dla celów korzytania z serwisu. Więcej informacji można znaleźć w Polityce prywatności oraz Regulaminie serwisu. Zamknięcie tego okienka potwierdza zapoznanie się z informacją o plikach cookies, akceptację polityki prywatności i regulaminu oraz sposobu wykorzystywania plików cookies w serwisie. Możesz zmienić ustawienia obsługi cookies w swojej przeglądarce.
Helper T cell responses that focus the TCR repertoire of responding clones provide experimental access to the mechanisms of clonal selection in vivo. Using TCRβ chain animals, we directly evaluate the extent of TCRα CDR3 diversity and the pMHCII binding attributes of individual antigen-specific Th cells. Here, we demonstrate that dominant clonotypes, as defined by TCR junctional sequence similarities,...
To examine the role of the TNF-R superfamily signaling protein TRAF2 in mature B cell development and NF-κB activation, conditionally TRAF2-deficient mice were produced. B cells lacking TRAF2 expression in these mice possessed a selective survival advantage, accumulated in the lymph nodes and splenic marginal zone, were larger in size, and expressed increased levels of CD21/35. These TRAF2-deficient...
During embryogenesis a developmental program leading to the formation of lymph nodes and Peyer's patches is initiated. We now show that lymph node-like structures as well as tertiary lymphoid structures can ectopically be induced by intradermal injection of newborn lymph node-derived cells. ICAM-1/VCAM-1-expressing stromal organizers, follicular dendritic cells, lymphatic endothelium, and HEVs in...
XLP is caused by mutations affecting SAP, an adaptor that recruits Fyn to SLAM family receptors. SAP-deficient mice recapitulate features of XLP, including increased T cell activation and decreased humoral responses post-infection. SAP-deficient T cells also show increased TCR-induced IFN-γ and decreased T H 2 cytokine production. We demonstrate that the defect in IL-4 secretion in SAP-deficient...
SAP is an adaptor mutated in X-linked lymphoproliferative disease. It plays a critical role in T helper 2 (T H 2) cytokine production. This function was suggested to reflect the capacity of SAP to associate with SLAM family receptors and enable tyrosine phosphorylation signaling by these receptors through SAP-mediated recruitment of Src-related kinase FynT. Here, we addressed by genetic means...
As a means of developing therapies that target the pathogenic T cells in multiple sclerosis (MS) without compromising the immune system or eliciting systemic side effects, we investigated the use of T-bet-specific antisense oligonucleotides and small interfering RNAs (siRNA) to silence T-bet expression in autoreactive encephalitogenic T cells and evaluated the biological consequences of this suppression...
Phagocytosis of apoptotic cells usually results in an anti-inflammatory state with inhibition of proinflammatory cytokines such as IL-12. How apoptotic cell-derived signals regulate IL-12 gene expression is not understood. We demonstrate that cell-cell contact with apoptotic cells is sufficient to induce profound inhibition of IL-12 production by activated macrophages. Phosphatidylserine could mimic...
Toll-like receptors (TLRs) detect microbial infection and play an essential role in the induction of innate and adaptive immune responses. The mechanisms of TLR-mediated control of adaptive immunity are not yet fully understood. Induction of dendritic cell (DC) maturation is essential for activation of naive T cells. Here, we demonstrate that TLR-induced DC maturation and migration to the lymph nodes,...
Caveolin-1 is a scaffolding protein that organizes and concentrates specific ligands within the caveolae membranes. We identified a conserved caveolin-1 binding motif in the HIV-1 transmembrane envelope glycoprotein gp41 and designed several synthetic peptides, referred to as CBD1, corresponding to the consensus caveolin-1 binding domain in gp41. In rabbits, these peptides elicit the production of...
Exposure of phosphatidylserine on the surface of apoptotic cells contributes to their removal in situ by quiet, noninflammatory, and nonimmunogenic mechanisms. In this issue of Immunity, describe a completely new mechanism for this effect that involves a novel zinc finger nuclear factor that inhibits IL-12 production.
The transcription factor C/EBPα is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBPα blocks the transition from the common myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBPα-deficient hematopoietic stem cells (HSCs) have increased expression of...
GM-CSF promotes homeostasis of myeloid cells. We report that GM-CSF upregulates mRNA and protein production of the soluble form of membrane bound VEGF receptor-1 (sVEGFR-1) in human monocytes. This sVEGFR-1 was biologically active, as cell-free supernatants from GM-CSF-stimulated monocytes blocked detection of endogenously expressed VEGF and inhibited endothelial cell migration and tube formation,...
The role of the thymus in HIV infection has been a matter of considerable debate. A new study by in this issue of Immunity provides the mechanism for reduced thymic output in HIV infection while illuminating the impact of recent thymic emigrants on peripheral T cell homeostasis.
Escape from adaptive T cell immunity through transmutation of viral antigenic structure is a cardinal feature in the pathogenesis of SIV/HIV infection and a major obstacle to antiretroviral vaccine development. However, the molecular determinants of this phenomenon at the T cell receptor (TCR)-antigen interface are unknown. Here, we show that mutational escape is intimately linked to the structural...
CD11c hi dendritic cells (DC) play an essential role during the initiation of cell-mediated immunity. Recently, CD11c lo CD45RB hi DC with regulatory properties have been described. However, the origins of regulatory DC are poorly understood. Here, we show that spleen-derived stromal cells promote selective development of CD11c lo CD45RB + ...
TRAIL receptor (TRAIL-R) signaling has been implicated in inducing apoptosis in tumor cells, but little is understood about its physiological function. Here, we report the generation and characterization of TRAIL-R -/- mice, which develop normal lymphocyte populations but possess enhanced innate immune responses. TRAIL-R -/- mice exhibited increased clearance of...
The Polycomb group (PcG) gene Bmi-1 has recently been implicated in the maintenance of hematopoietic stem cells (HSC) from loss-of-function analysis. Here, we demonstrate that increased expression of Bmi-1 promotes HSC self-renewal. Forced expression of Bmi-1 enhanced symmetrical cell division of HSCs and mediated a higher probability of inheritance of stemness through cell division. Correspondingly,...
The supply of naive T cells by the thymus normally requires precursor T cell proliferation within the thymus and would be particularly important in the setting of HIV infection when both naive and memory T cells are progressively depleted. As a robust, quantitative index of intrathymic proliferation, the ratio of different T cell receptor excision circles (TRECs), molecular markers of distinct T cell...
Podaj zakres dat dla filtrowania wyświetlonych wyników. Możesz podać datę początkową, końcową lub obie daty. Daty możesz wpisać ręcznie lub wybrać za pomocą kalendarza.