Mouse and human dendritic cell subtypes (original) (raw)
Related papers
The Induction of Tolerance by Dendritic Cells That Have Captured Apoptotic Cells
Journal of Experimental Medicine, 2000
What makes a protein immunogenic, particularly for strong T cell-mediated immunity? To a first approximation, this determination seems to be made by dendritic cells (DCs). Immature DCs, as in skin (1-4), lung (5), blood (6, 7), and spleen (7, 8), take up proteins, immune complexes, microbes, and dying cells. However, in order to use these antigens to stimulate a T cell response, the DCs must undergo a characteristic process of terminal differentiation called "maturation." The known stimuli for DC maturation are numerous and include inflammatory cytokines, CD40 ligand (CD40L), viral and microbial constituents such as doublestranded RNA and LPS, and certain CpG oligonucleotides. DC Maturation as a Control Point in the Initiation of Immunity Maturation changes DCs in many ways that help explain their potent immunogenicity. Examples include de novo expression of T cell costimulatory molecules like CD86 (9, 10); the capacity to produce IL-12 (11, 12) and resist immunosuppression by IL-10 (13); the development of a new repertoire of chemokine receptors, especially CCR7 (14-17), that guide entry into lymphatics and migration to the T cell areas (18); the production of DC survival and stimulatory molecules like CD40 and TNF-related activation-induced cytokine receptor (TRANCE-R) (19, 20); and a redistribution of MHC class II molecules from lysosomes to the cell surface (21, 22). Recently, it has been found (Inaba, K.
Frontiers in Immunology, 2012
The last decades of Nobel prize-honored research have unequivocally proven a key role of dendritic cells (DCs) at controlling both T cell immunity and tolerance. A tight balance between these opposing DC functions ensures immune homeostasis and host integrity. Its perturbation could explain pathological conditions such as the attack of self tissues, chronic infections, and tumor immune evasion. While recent insights into the complex DC network help to understand the contribution of individual DC subsets to immunity, the tolerogenic functions of DCs only begin to emerge. As these consist of many different layers, the definition of a "tolerogenic DC" is subjected to variation. Moreover, the implication of DCs and DC subsets in the suppression of autoimmunity are incompletely resolved. In this review, we point out conceptual controversies and dissect the various layers of DC-mediated T cell tolerance. These layers include central tolerance, Foxp3 + regulatory T cells (Tregs), anergy/deletion and negative feedback regulation. The mode and kinetics of antigen presentation is highlighted as an additional factor shaping tolerance. Special emphasis is given to the interaction between layers of tolerance as well as their differential regulation during inflammation. Furthermore, potential technical caveats of DC depletion models are considered. Finally, we summarize our current understanding of DC-mediated tolerance and its role for the suppression of autoimmunity. Understanding the mechanisms of DC-mediated tolerance and their complex interplay is fundamental for the development of selective therapeutic strategies, e.g., for the modulation of autoimmune responses or for the immunotherapy of cancer.
The Role of Dendritic Cells in Central Tolerance
Immune Network, 2015
Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions.
Nature Immunology, 2005
The maturation status of dendritic cells (DCs) determines whether they prime or tolerize T cells. We targeted ovalbumin peptide exclusively to DCs in situ using an antibody to DEC-205 and studied the interaction of DCs with naive CD4 + T cells in tolerizing or priming conditions. We used two-photon microscopy to simultaneously track antigen-specific OT-II T cells, nonspecific T cells and DCs in lymph nodes of living mice. In both tolerance and immunity, OT-II cells arrested on DCs near high endothelial venules beginning shortly after extravasation and regained their baseline speed by 18 h. Thus, early antigen-dependent T cell arrest on DCs is a shared feature of tolerance and priming associated with activation and proliferation.
Induction of peripheral CD4+ T-cell tolerance and CD8+ T-cell cross-tolerance by dendritic cells
European Journal of Immunology, 2009
DC can present and cross-present self-antigens to autoreactive CD4 1 and CD8 1 T cells, respectively, and incapacitate them by inducing anergy, deletion or converting them into Treg. In this review, we summarize the recent progress in immune tolerance research, which has been achieved by employing antigen-and TCR-transgenic mice. We cover the numerous discoveries that have furthered our knowledge of the DC subsets and maturation pathways involved in tolerance; the signals, such as CD70, TGF-b, B7-H1/PD-L1, which dictate the decision between immunity and tolerance; and the in vivo role of DC in the maintenance of CD4 1 T-cell tolerance and CD8 1 T-cell cross-tolerance.
The anatomy of T-cell activation and tolerance
Proceedings of the National Academy of Sciences, 1996
The mammalian immune system must specifically recognize and eliminate foreign invaders but refrain from damaging the host. This task is accomplished in part by the production of a large number of T lymphocytes, each bearing a different antigen receptor to match the enormous variety of antigens present in the microbial world. However, because antigen receptor diversity is generated by a random mechanism, the immune system must tolerate the function of T lymphocytes that by chance express a self-reactive antigen receptor. Therefore, during early development, T cells that are specific for antigens expressed in the thymus are physically deleted. The population of T cells that leaves the thymus and seeds the secondary lymphoid organs contains helpful cells that are specific for antigens from microbes but also potentially dangerous T cells that are specific for innocuous extrathymic self antigens. The outcome of an encounter by a peripheral T cell with these two types of antigens is to a great extent determined by the inability of naive T cells to enter nonlymphoid tissues or to be productively activated in the absence of inflammation.