Macrophages are not only host cells for many pathogens, but also fulfill several key functions in the innate and adaptive immune response, including the release of pro- and anti-inflammatory cytokines, the generation of organic and inorganic autacoids, the phagocytosis and killing of in ...
Understanding the regulation of distinct dendritic cell (DC) function and differentiation pathways is important in many physiological and pathophysiological processes. This includes infectious and neoplastic diseases, vaccination and immunotherapy, allograft rej ...
Diversity in macrophage responsiveness to inflammatory stimuli has resulted in the description of a new paradigm wherein macrophages are referred to as polarized into one of two distinct phenotypes, classically activated (M1) macrophages and alternatively activated (M2) macr ...
The efficient degradation of internalized particulate matter is a principal objective of the macrophage’s phagosome. Assessment of the true hydrolytic capacity within the phagosomal lumen is often difficult as it is subject to many factors beyond recruitment of lysosomal hydrola ...
The ability to manipulate in vitro cultured dendritic cells (DCs) by transfection represents an attractive strategy to load these antigen-presenting cells with genetic material encoding various immunogenic epitopes. The gene transfer approach can also be applied to DCs with the aim ...
Tracking antigen-specific cytotoxic T lymphocyte (CTL) function in vivo can be difficult due to the need to monitor the presence and subsequent destruction of antigen-bearing target cells. In this report, we describe a simple method using the fluorescent dye 5-(and 6-) carboxyfluoresce ...
Two-photon microscopy makes it possible to image in real-time fluorescently labeled cells located in deep tissue environments. We describe a procedure to visualize the behavior of lymph node T cells during either priming or tolerance, in live, anesthetized mice. Intravital imaging of T ly ...
Radiolabeled antibodies are commonly administered to patients, and their biodistribution to tumor and normal tissues is routinely quantitated by nuclear medicine scanning for dosimetry (1). Only a few studies have examined the uptake of radiolabeled immunotoxins into tumors or n ...
Since the discovery of cross priming by Bevan (1) nearly thirty years ago, a large amount of work has focused on defining the mechanisms that account for this in vivo phenomenon. Following the discovery that the majority of major histocompatibility complex (MHC-I)-bound peptides are derived f ...
The thymus contributes to the regulation of tolerance and the prevention of autoimmunity at many levels. First, auto-reactive CD4+ and CD8+ T cells are clonally deleted during negative selection in the thymus, establishing central tolerance. The unique expression of the AIRE (autoimmu ...
Induction of mixed chimerism (i.e., coexistence of donor and recipient hematopoietic cells) through transplantation of allogeneic donor bone marrow under appropriate host conditioning, is one of the most reliable strategies to induce transplantation tolerance. Robust toler ...
Monoclonal antibodies (MAb) have been shown to be effective in inducing immune tolerance in transplantation and autoimmunity. Several different MAb have tolerogenic properties and their effect has been studied in a range of experimental animal models and, in some cases, in clinical tri ...
Naturally arising CD4+CD25+ regulatory T (Treg) cells can be exploited to establish immunologic tolerance to allogeneic transplants. In vivo exposure of CD4+CD25+ T cells from normal na�ve mice to alloantigen in a T cell-deficient environment elicits spontaneous expansion of alloan ...
Initial studies in our laboratory were focused on the use of dendritic cells (DC) genetically modified to express Th2-derived cytokines (i.e., interleukin -4 and IL-10) or apoptotic proteins (i.e., Fas Ligand ) to reduce inflammation in a mouse model of experimentally induced arthritis. Exo ...
Dendritic cells (DC) are extremely potent antigen-presenting cells, which can prime both na�ve CD4+ and CD8+ T lymphocytes. In their immature state, DC continuously sample and process antigens from the surrounding environment, but only mature DC express sufficient levels of costimula ...
Serological analysis of tumor antigens by recombinant cDNA expression cloning (SEREX) allows the systematic cloning of tumor antigens recognized by the spontaneous autoantibody repertoire of cancer patients. For SEREX, cDNA expression libraries are constructed from fresh t ...
Due to the existence of the truly specific tumor antigen idiotype in multiple myeloma and based on encouraging data from dendritic cell vaccinated B-cell non-Hodgkin’s lymphoma (NHL) patients, dendritic cell-based vaccination was first initiated in myeloma patients in 1995. This ove ...
Regulatory T-cells play a central role in the maintenance of the immunological balance and are powerful inhibitors of T-cell activation both in vivo and in vitro. The enhancement of suppressor-cell function might be a target for immunotherapeutic approaches for the treatment of immune- ...
Attempts to treat patients with tumor-reactive cytotoxic T-lymphocytes (CTL) have been limited. This is due to the difficulty of isolating and expanding functionally active T-cells, which are present at extremely low frequencies in the peripheral blood. Recently developed multim ...
Advances in immunological monitoring provide the means to track tumor antigen-specific cytotoxic T-lymphocytes (CTL) in humans after adoptive transfer with greater specificity and sensitivity than before. Novel tools can be used not only to detect antigen-specific CTL, but also to e ...