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Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response.We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis. [ABSTRACT FROM AUTHOR]

Abstract: The immune system has evolved to coordinate responses against numerous invading pathogens and simultaneously remain silent facing self-antigens and those derived from commensal organisms. But, if both processes are not maintained in strict balance, a potential threat can emerge due to the risk of chronic inflammation and/or autoimmunity development. Therefore, there is a negative immune regulation where tolerogenic dendritic cells (tDCs) participate actively. Under steady-state conditions, tDC are notably involved in the elimination of autoreactive T cells at the thymus, and in the control of T cells specific to self and harmless antigens in the periphery. But in the presence of foreign antigens in an inflammatory milieu, dendritic cells (DCs) mature and induce T cells activation and their migration to B cell areas to assist in antibody production. Additionally, there are other factors such as infections, anti tumoral immune responses, trauma-mediated disruption, etc. that may induce alterations in the balance between tolerogenic and immunogenic functions of DCs and instigate the development of autoimmune diseases (ADs). Therefore, in recent years, DCs have emerged as therapeutic targets to control of ADs. Diverse strategies in vitro and/or in animal models of ADs have explored the tolerogenic functions of DCs and demonstrated their feasibility to prevent or control an autoimmune process, but still leaving a void in their application in clinical assays. The purpose of this paper is to give a general overview of the current literature on the significance of tDCs in tolerance maintenance to self and innocuous antigens, the most relevant alterations involved in the pathophysiology of ADs, the cellular and molecular mechanisms involved in their tolerogenic function and the current strategies used to exploit their tolerogenic potential. [Copyright &y& Elsevier]

Please cite this paper as: Increased regulatory T-cell frequencies in patients with advanced melanoma correlate with a generally impaired T-cell responsiveness and are restored after dendritic cell-based vaccination. Experimental Dermatology 2010; 19: e213-e221. Abstract: Naturally occurring CD4+ CD25+ regulatory T-cell (Treg) activity is assumed to facilitate tumor development and progression. To elucidate the possible role of Tregs in the course of melanoma progression, we analysed the frequency of Tregs in the peripheral blood of patients at melanoma stages I-IV and in patients at melanoma stage IV that underwent dendritic cell (DC)-based immunotherapy. Using CD25, Foxp3, CD127 and HLA-DR as Treg associated markers, we observed increased Treg frequencies in patients at the late melanoma stage (stage IV) when compared to healthy donors. Accumulation of Tregs in patients with progressed melanoma correlated with a general reduction of T-cell responsiveness to the recall antigens tetanus toxoid and tuberculin-GT. However, DC-based immunotherapy not only restored antigen-specific immunity, but also decreased the frequency of Tregs in peripheral blood of patients with melanoma. These findings indicate that tumor progression in patients with melanoma result in general immunosuppression that is associated with Treg expansion in the periphery and can be overcome by DC-based vaccination. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Enhanced T-cell activation by immature dendritic cells loaded with HSP70-expressing heat-killed melanoma cells. Experimental Dermatology 2010; 19: 108–116. Vaccination protocols that utilize dendritic cells (DCs) to elicit therapeutic immunity against tumors are the subject of intense research. Given that the capacity of DCs to cross-present antigens is physiologically low, there is considerable interest to develop strategies that enhance that pathway. In order to best exploit the enhanced cross-presentation of antigens bound to heat shock protein 70 (HSP70), we analysed melanoma cell preparations for their HSP70 expression. Western blotting revealed strong upregulation of HSP70 after heat-killing in contrast to UV-B irradiation. When the uptake of heat-killed necrotic cells by DCs at various levels of maturation was assessed, 61 ± 7% of immature DCs (iDCs) internalized fluorescence-labelled necrotic material. Apoptotic material from UV-B-irradiated cells was internalized by only 48 ± 5% of iDCs. Maturation-inducing cytokines did not affect the uptake when added simultaneously with the tumor cell preparations. Loading DCs with heat-necrotic or apoptotic melanoma cells slightly reduced CD83 expression while leaving CD208 (DC-LAMP) expression unchanged. As determined by IFN-γ-detecting enzyme-linked-immunospot assays, iDCs loaded with heat-killed melanoma cells activated autologous T cells most effectively when used without any further maturation, whereas DCs loaded with apoptotic material required maturation. In conclusion, HSP70-expressing melanoma cells could be generated by heat-killing. Loading iDCs with heat-killed melanoma cells resulted in a superior priming of autologous T cells in vitro. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that are critical for the generation of effective cytotoxic T lymphocyte (CTL) responses; however, their function and phenotype are often defective or altered in tumor-bearing hosts, which may limit their capacity to mount an effective tumor-specific CTL response. In particular, the manner in which exogenous tumor antigens are acquired, processed, and cross-presented to CD8 T cells by DCs in tumor-bearing hosts is not well understood, but may have a profound effect on antitumor immunity. In this paper, we have examined the role of DCs in the cross-presentation of tumor antigen in terms of their subset, function, migration, and location with the intention of examining the early processes that contribute to the development of an ineffective anti-tumor immune response. [ABSTRACT FROM AUTHOR]

The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment. [ABSTRACT FROM AUTHOR]

Cortical F-actin plays important roles during HIV-1 infection. A recent paper in Cell highlights the involvement of F-actin in enhancing dendritic cell (DC)-mediated HIV-1 infection of T cells. Such a critical mechanism of HIV-1 trans -enhancement between human DCs and T cells had not been analyzed in molecular detail before this work. [ABSTRACT FROM AUTHOR]

Chronic inflammation of the adipose tissue (AT) is a critical component of obesity-induced insulin resistance and type 2 diabetes. Adipose tissue immune cells, including AT macrophages (ATMs), AT dendritic cells (ATDCs), and T cells, are dynamically regulated by obesity and participate in obesity-induced inflammation. Among AT resident immune cells, ATDCs are master immune regulators and engage in crosstalk with various immune cells to initiate and regulate immune responses. However, due to confounding markers and lack of animal models, their exact role and contribution to the initiation and maintenance of AT inflammation and insulin resistance have not been clearly elucidated. This paper reviews the current understanding of ATDCs and their role in obesity-induced AT inflammation. We also provide the potential mechanisms by which ATDCs regulate AT inflammation and insulin resistance in obesity. Finally, this review offers perspectives on ways to better dissect the distinct functions and contributions of ATDCs to obesity. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) 'pulsed' with an appropriate antigen may elicit an antitumour immune response in mouse models. However, while attempting to develop a DC immunotherapy protocol for the treatment of breast cancer based on the tumour-associated MUC1 glycoforms, we found that unpulsed DCs can affect tumour growth. Protection from RMA-MUC1 tumour challenge was achieved in C57Bl/6 MUC1 transgenic mice by immunising with syngeneic DCs pulsed with a MUC1 peptide. However, unpulsed DCs gave a similar level of protection, making it impossible to evaluate the effect of immunisation of mice with DCs pulsed with the specific peptide. Balb/C mice could also be protected from tumour challenge by immunisation with unpulsed DCs prior to challenge with murine mammary tumour cells (410.4) or these cells transfected with MUC1 (E3). Protection was achieved with as few as three injections of 50,000 naïve DCs per mouse per week, was not dependent on injection route, and was not specific to cell lines expressing human MUC1. However, the use of Rag2-knockout mice demonstrated that the adaptive immune response was required for tumour rejection. Injection of unpulsed DCs into mice bearing the E3 tumour slowed tumour growth. In vitro, production of IFN-gamma and IL-4 was increased in splenic cells isolated from mice immunised with DCs. Depleting CD4 T cells in vitro partially decreased cytokine production by splenocytes, but CD8 depletion had no effect. This paper shows that naïve syngeneic DCs may induce an antitumour immune response and has implications for DC immunotherapy preclinical and clinical trials. [ABSTRACT FROM AUTHOR]

Inappropriate T cell responses cause the four classical types of hypersensitivity immune reactions. All of these can target the kidney and cause distinct forms of glomerulonephritis. CD4+ T cells can mediate glomerular immunopathology by cytokine secretion, by activating effector cells such as macrophages or by inducing auto-antibodies or immune-complexes. Cytotoxic CD8+ T cell responses and failure of regulatory T cells may represent two additional types of anti-renal hypersensitivity. T cell activation is critically dependent on dendritic cells (DC), whose role in renal disease appears to be protective, but underlying mechanisms are largely unknown. In this paper, we summarized mechanistic information from rodent models on the roles of DC and T cells in glomerular immunopathology. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes the histopathological features and cellular distribution of T lymphocytes (CD3), B cells (CD79), follicular dendritic cells (FDC) and macrophages (alpha-1-antitrypsin, lysozyme) in lymphoid aggregates (Kisselev nodules) found in the lung, kidney and liver of wild boar (Sus scrofa L.). The distribution of immunoreactive cells, tested for antibodies, was similar to that found in the cortex of lymph nodes: lymphoid follicles with germinal centers mainly consisting of CD79+ B cells with sparse interfollicular tissue (CD3+ T lymphocytes). This finding and the association of these structures with helminthic infections suggests that local humoral immunity is central to the organism’s response to parasitic challenge. The presence of follicular dendritic cells confirms the high degree of organization of these lymphoid-like structures. The role of other pathogenic factors and the induction of chronic inflammatory reaction in these ectopic lymphoid sites is also discussed. [Copyright &y& Elsevier]

In the early phases of an immune response, T cells of appropriate antigen specificity become activated by antigen-presenting cells in secondary lymphoid organs. Two-photon microscopy imaging experiments have shown that this stimulation occurs in distinct stages during which T cells exhibit different motilities and interactions with dendritic cells (DCs). In this paper, we utilize the Cellular Potts Model, a model formalism that takes cell shapes and cellular interactions explicitly into account, to simulate the dynamics of, and interactions between, T cells and DCs in the lymph node paracortex. Our three-dimensional simulations suggest that the initial decrease in T-cell motility after antigen appearance is due to ‘stop signals’ transmitted by activated DCs to T cells. The long-lived interactions that occur at a later stage can only be explained by the presence of both stop signals and a high adhesion between specific T cells and antigen-bearing DCs. Furthermore, our results indicate that long-lasting contacts with T cells are promoted when DCs retract dendrites that detect a specific contact at lower velocities than other dendrites. Finally, by performing long simulations (after prior fitting to short time scale data) we are able to provide an estimate of the average contact duration between T cells and DCs.Immunology and Cell Biology (2007) 85, 306–314. doi:10.1038/sj.icb.7100054; published online 10 April 2007 [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-γ upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, ‘in situ DC-vaccine’ that is readily applicable in the clinic without prior knowledge of tumour antigens.British Journal of Cancer (2006) 95, 896–905. doi:10.1038/sj.bjc.6603341 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Background: The purpose of the present paper was to investigate dendritic cell (DC) and T-cell functions in patients with chronic hepatitis B (CHB) and determine whether therapeutic DC vaccines could restore T-cell function in those patients in vitro. Methods: Twelve patients with CHB and 10 normal control subjects with positivity for antibodies to hepatitis B surface and core antigens (anti-HBs and anti-HBc positivity) were enrolled in the present study. Phenotype analysis and allogeneic mixed lymphocyte reaction assay of DC from CHB patients and normal controls were made in the absence or presence of a cocktail of cytokines: interleukin-1β (IL-1β), prostaglandin E2 (PGE2), IL-6 and tumor necrosis factor-α (TNF-α). Autologous T-cell proliferation assays and the enzyme-linked immunospot (ELISPOT) method for detecting interferon-γ (IFN-γ)-producing CD8+ T cells were used to evaluate the efficacy of DC loaded in vitro with HBsAg or HBcAg. Results: The DC from CHB patients had a lower expression of costimulatory molecules CD80, CD86 and impaired allogeneic mixed lymphocyte reaction capacity compared to those from normal controls. However, the impaired DC function could be restored partially by cytokine cocktail supplemented in vitro. Mature DC loaded with HBsAg or HBcAg showed a greater capacity for autologous T-cell proliferation and antigen-specific IFN-γ production than immature DC. Moreover, as a DC -loading antigen, HBcAg was more immunogenic than HBsAg. Conclusions: The impaired function of DC in patients with CHB may be restored by supplementation in vitro with a cocktail of cytokines, and therapeutic DC vaccines might be effective to treat CHB infection in humans. [ABSTRACT FROM AUTHOR]

By substituting the heavy chain constant region of IgM and IgD with that of IgG, IgA or IgE, immunoglobulin class switching endows antibodies with novel effector functions that enhance the ability of the immune system to effectively clear invading pathogens. Plasmacytoid dendritic cells critically link innate immunity with adaptive immunity by producing massive amounts of type 1 IFN in response to viruses. We have recently found that type 1 IFN triggers class switching by inducing myeloid dendritic cells to upregulate the expression of BAFF and APRIL, two powerful B cell-activating molecules. In this paper, we propose that IFN-producing plasmacytoid dendritic cells modulate class switching by activating B cells through both T cell-dependent and T cell-independent pathways. A better understanding of these pathways may facilitate the development of novel antiviral vaccine strategies and aid in identifying new therapies for antibody-mediated autoimmune disorders, such as lupus. [ABSTRACT FROM AUTHOR]

The paper reviews the literature reports on low molecular weight (LMW) sensitizers that are commonly encountered in the work environment as well as on the major mechanisms responsible for their effect on the immune cells of the respiratory tract. Current studies have focused on: LMW-antigens; the role of airway epithelial and dendritic cells (DCs); activation of naive helper T (Th) cells by DCs; naive B cell-effector Th2 cell interactions; and activation of mast cells by LMW asthmogens. A better understanding of the pathogenesis of occupational asthma due to LMW asthmogens should facilitate the development of better diagnostics and the improvement of strategies for disease surveillance and intervention. [ABSTRACT FROM AUTHOR]

Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular, the role of DCs in the generation of regulatory T cells is highlighted. [ABSTRACT FROM AUTHOR]

During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity and in selected patients to tumor regression. However, the majority of clinical trials are still in phase I, and interpretations are hampered by pronounced variation in study design related to technical aspects of DC preparation, treatment and schedule, monitoring of immune response, and clinically relevant endpoints, including toxicity and response evaluation. This paper aims to review the technical aspects and clinical impact of vaccination trials, focusing on the generation of DC-based vaccines, evaluation of immunologic parameters and design of clinical trials necessary to meet the need for good laboratory and clinical practice. [ABSTRACT FROM AUTHOR]

Presents abstracts of research papers on dendritic cells, published in the December 2002 supplement of 'Immunology.' 'Dendritic cell biology,' by M. Moser; 'Investigating the MHC-restriction of CD4[sup+]CD25[sup+] regulatory T cells,' by L.R. Ambrose.

Dendritic cells (DCs) are recognized as the sole professional antigen-presenting cells capable of priming naive T cells of the helper and cytotoxic phenotypes. This property is presently exploited with success in vaccinal strategies against pathogens or tumor cells that otherwise escape immune recognition, but the repeated infusions of ex vivo expanded and sensitized DCs are usually required to achieve protection. In this paper, we demonstrate that liposomal antigens can efficiently relay and propagate the action of DCs, inducing a strong long-term response against their associated antigen. Their effect is mainly achieved by improving the ex vivo loading of DCs and by efficiently channeling the activation stimulus into the induction of effector function. This is demonstrated by the sustained immunoglobulin production as well as by the sustained lymphoproliferation and the increased cytokine secretion that can be achieved upon restimulation of DC-primed immune cells with limited amount of liposomal antigenic material. Being well-tolerated and easily prepared, liposomal antigens could therefore be expected to significantly contribute to the efficiency and to a more general utilization of the highly promising but rather cumbersome DC-based immunotherapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is the most common primary bone tumor and has a poor prognosis. Therefore, it is important to understand the mechanism of the development of osteosarcoma to overcome therapy resistance. Several mathematical models have been developed to study the initiation and progression of many cancer types. However, there are currently no mathematical models for the progression of osteosarcoma, to the best of our knowledge. In this work, we develop a data-driven mathematical model to analyze the impact of the immune cell interactions on the growth of osteosarcoma tumors that have distinct immune patterns. Our model provides a foundation for investigating the effect of various treatments on the dynamics of key players in the primary tumor, including immune cells and cytokines, and ultimately the whole tumor. As the immune system has a significant role in tumor progression, in this paper, we develop a data-driven mathematical model to study the interactions between immune cells and the osteosarcoma microenvironment. Osteosarcoma tumors are divided into three clusters based on their relative abundance of immune cells as estimated from their gene expression profiles. We then analyze the tumor progression and effects of the immune system on cancer growth in each cluster. Cluster 3, which had approximately the same number of naive and M2 macrophages, had the slowest tumor growth, and cluster 2, with the highest population of naive macrophages, had the highest cancer population at the steady states. We also found that the fastest growth of cancer occurred when the anti-tumor immune cells and cytokines, including dendritic cells, helper T cells, cytotoxic cells, and IFN- γ , switched from increasing to decreasing, while the dynamics of regulatory T cells switched from decreasing to increasing. Importantly, the most impactful immune parameters on the number of cancer and total cells were the activation and decay rates of the macrophages and regulatory T cells for all clusters. This work presents the first osteosarcoma progression model, which can be later extended to investigate the effectiveness of various osteosarcoma treatments. [ABSTRACT FROM AUTHOR]

The mechanisms through which tumor antigen-specific T cells are elicited in natural or chemotherapy-induced immunosurveillance have been elusive. In this issue of Cancer Cell , two papers by Broz and colleagues and Ruffell and colleagues delineate an important role for a specific dendritic cell subset characterized by CD103 expression, dependence on transcription factors Batf3 and Irf8, and interleukin-12 production. [ABSTRACT FROM AUTHOR]

The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD). The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathogenesis is still the subject of emerging research. A paper by Botelho and colleagues in the current issue of Respiratory Research investigates the importance of dendritic cell recruitment in cigarette-smoke induced acute and chronic inflammation in mice. Dendritic cells of the healthy lung parenchyma and airways perform an important sentinel function and regulate immune homeostasis. During inflammatory responses the function and migration pattern of these cells is dramatically altered but the underlying mechanisms are incompletely understood. Botelho and colleagues demonstrate here the importance of IL-1R1/IL-1α related mechanisms including CCL20 production in cigarette-smoke induced recruitment of dendritic cells and T cell activation in the mouse lung. [ABSTRACT FROM AUTHOR]

Epidermal Langerhans cells are dendritic bone marrow-derived cells which synthesize and express Ia antigens. During the past decade, in vitro studies have demonstrated that they play a critical role in the induction of many types of T-cell responses. Specifically, Langerhans cells are effective antigen-presenting cells in allogeneic and antigen specific proliferative and cytotoxic T-cell responses. This paper reviews these functions and suggests areas of future investigations into the mechanisms involved in T-cell activation by Langerhans cells. [ABSTRACT FROM AUTHOR]

In a recent paper published in Cell Host & Microbe, Dasgupta et al. (2014) demonstrate that a component of the gut microbiota, Bacteroides fragilis, induces IL-10-producing regulatory T cells by driving TLR2-dependent plasmacytoid dendritic cell activation. [Copyright &y& Elsevier]

Dendritic cells induce the activation of CD8 and CD4 T cells by presenting antigenic peptides on MHC class I and class II molecules, respectively. In a recent Science paper, reveal that these tasks are handled by distinct populations of dendritic cells in vivo. [Copyright &y& Elsevier]

Discusses a paper by G. Willimsky and T. Blankenstein which showed that sporadic tumors in mice, against which the immune system initially reacts, nevertheless manage to spread by molding the killer T cells into a state that tolerates them. Implications for the debate on whether the development of sporadic, nonviral tumors is really affected by so-called immunoediting; Concurrence of both sides of the controversy that both virus-induced and sporadic tumors do elicit immune responses, and that T-cell responses protect against viral carcinogenesis; Variation in the natural ability of tumors to activate dendritic cells; Need for tumors to be sensed by an exquisitely sensitive sentinel system, the dendritic cell network.

Developing an immunotherapy to keep human immunodeficiency virus type 1 (HIV-1) replication suppressed while discontinuing highly active antiretroviral therapy (HAART) is an important challenge. In the present work, we evaluated in vitro whether dendritic cells (DC) electroporated with gag mRNA can induce HIV-specific responses in T cells from chronically infected subjects. Monocyte-derived DC, from therapy-naïve and HAART-treated HIV-1-seropositive subjects, that were electroporated with consensus codon-optimized HxB2 gag mRNA efficiently expanded T cells, secreting gamma interferon (IFN-γ) and interleukin 2 (IL-2), as well as other cytokines and perforin, upon restimulation with a pool of overlapping Gag peptides. The functional expansion levels after 1 week of stimulation were comparable in T cells from HAART-treated and treatment-naïve patients and involved both CD4+ and CD8+ T cells, with evidence of bifunctionality in T cells. Epitope mapping of p24 showed that stimulated T cells had a broadened response toward previously nondescribed epitopes. DC, from HAART-treated subjects, that were electroporated with autologous proviral gag mRNA equally efficiently expanded HIV-specific T cells. Regulatory T cells did not prevent the induction of effector T cells in this system, whereas the blocking of PD-L1 slightly increased the induction of T-cell responses. This paper shows that DC, loaded with consensus or autologous gag mRNA, expand HIV-specific T-cell responses in vitro. [ABSTRACT FROM AUTHOR]

The article focuses on research on immune responses, regulatory T cells and T-cell signaling. Papers discussed which were published in other periodicals include "Dendritic Cell Stimulation By Mycobacterial Hsp70 is Mediated Through CCR5," by R. A. Floto et al and "Alterations in CD46-Mediated Tr1 Regulatory T Cells in Patients With Multiple Sclerosis," by A. L. Astier et al.

The article focuses on a research paper investigating whether it is possible to induce antitumor responses in vivo in cancer patients by activating natural killer T (NKT) cells, which are induced to proliferate by dendritic cells. The patients experienced temporary inflammatory symptoms as well as respiratory symptoms in individuals with pulmonary metastases. The study offers clinical evidence that NKT cells can bridge innate and acquired immunity to induce secondary antitumor immune responses.

Presents research highlights from the 'Nature' family of journals as of April 5, 2001. Study published in 'Nature Biotechnology,' which describes a prototype biosensor array of ribozymes; Papers published in 'Nature Medicine,' which pinpoint the key molecules involved in the follicular dendritic cell capture mechanism; Article published in 'Nature Immunology,' which explores the generation of T-cells; Others.