Abstract：
:Adoptive cell therapy (ACT) destroys tumors with infused cytotoxic T lymphocytes (CTLs). Although successful in some settings, ACT is compromised due to impaired survival or functional inactivation of the CTL. To better understand the mechanisms involved, we have exploited a mouse model of leukemia expressing ovalbumin as a tumor neoantigen to address these questions: (i) Is CTL impairment during ACT antigen specific? (ii) If yes, which are the antigen-presenting cells responsible? (iii) Can this information assist the development of complementary therapies to improve ACT? Our results indicate that the target (tumor) cells, not cross-presenting cells, are the main culprits of antigen-specific CTL inactivation. We find that the affinity/avidity of the CTL-tumor cell interaction has little influence on ACT outcomes, while tumor density is a major determinant. Reduction of tumor burden with mild non-lymphoablative and non-inflammatory chemotherapy can dramatically improve the efficacy of ACT and may minimize side-effects. We propose a general mechanism for the inactivation of anti-self CTL in the same tissues where the activity of anti-foreign CTL is preserved, based on the density of target cells. This mechanism, which we tentatively call stunning, may have evolved to protect infected sites from self-destruction and is exploited by tumors to inactivate CTL.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Villadangos JAdoi
10.1111/imr.12433subject
Has Abstractpub_date
2016-07-01 00:00:00pages
169-82issue
1eissn
0105-2896issn
1600-065Xjournal_volume
272pub_type
杂志文章,评审abstract：:Highlights in a 4-decade exploration of lymphocyte differentiation begin with comparative studies in birds and mammals leading to recognition of the separate T- and B-cell differentiation pathways and their cooperative interaction. The global effects of aborting IgM B-cell development with anti-mu antibodies indicated...
journal_title：Immunological reviews
pub_type： 历史文章,杂志文章,评审
doi：10.1034/j.1600-065x.2002.18515.x
更新日期：2002-07-01 00:00:00
abstract：SUMMARY:This volume covers many topics in the field of T-cell costimulation. The need for such a volume is testament to the growth of the field. From its beginning as a concept in the 1980s, we have now progressed to the point where many molecules now have functionally defined roles in T-cell costimulation. In addition...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2009.00780.x
更新日期：2009-05-01 00:00:00
abstract：:Regulatory T cells (Tregs) are critical to the human immune system, providing appropriately scaled immune responses and mediating peripheral tolerance. A central role for forkhead box protein 3 (FoxP3)(+) Tregs has been shown in the pathogenesis of mechanistically diverse central nervous system (CNS) diseases from aut...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2012.01130.x
更新日期：2012-07-01 00:00:00
abstract：:Since the discovery that the recombination-activating gene (RAG) proteins were capable of transposition in vitro, investigators have been trying to uncover instances of transposition in vivo and understand how this transposase has been harnessed to do useful work while being inhibited from causing deleterious chromoso...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2004.00161.x
更新日期：2004-08-01 00:00:00
abstract：:CD69 has been known as an early activation marker of lymphocytes; whereas, recent studies demonstrate that CD69 also has critical functions in immune responses. Early studies using human samples revealed the involvement of CD69 in various inflammatory diseases including asthma. Moreover, murine disease models using Cd...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12559
更新日期：2017-07-01 00:00:00
abstract：:Immune responses to gastrointestinal nematodes have been studied extensively for over 80 years and intensively investigated over the last 30-40 years. The use of laboratory models has led to the discovery of new mechanisms of protective immunity and made major contributions to our fundamental understanding of both inn...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12188
更新日期：2014-07-01 00:00:00
abstract：:Apoptosis is an important component of normal tissue physiology, and the prompt removal of apoptotic cells is equally essential to avoid the undesirable consequences of their accumulation and disintegration. Professional phagocytes are highly specialized for engulfing apoptotic cells. The recent ability to track cells...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12537
更新日期：2017-05-01 00:00:00
abstract：:Interleukin (IL)-33 is a key cytokine involved in type 2 immunity and allergic airway diseases. Abundantly expressed in lung epithelial cells, IL-33 plays critical roles in both innate and adaptive immune responses in mucosal organs. In innate immunity, IL-33 and group 2 innate lymphoid cells (ILC2s) provide an essent...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12552
更新日期：2017-07-01 00:00:00
abstract：:Inflammasomes are multiprotein complexes that control the maturation and production of interleukin-1 family members and play crucial roles in host defense against pathogens. However, dysregulated activation of inflammasomes is associated with intense inflammation, leading to the development of inflammatory diseases. T...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12613
更新日期：2018-01-01 00:00:00
abstract：:Hepatitis B virus (HBV) is a major human pathogen that causes chronic infection and life-threatening liver diseases in millions of individuals. While pathological and epidemiological consequences of clinically evident HBV infections are well recognized, there is no similar knowledge on an asymptomatic, silently progre...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-0528.2002.017406.x
更新日期：2000-04-01 00:00:00
abstract：:The response to pathogens and damage in plants and animals involves a series of carefully orchestrated, highly evolved, molecular mechanisms resulting in pathogen resistance and wound healing. In metazoans, damage- or pathogen-associated molecular pattern molecules (DAMPs, PAMPs) execute precise intracellular tasks an...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2007.00579.x
更新日期：2007-12-01 00:00:00
abstract：:Over the past two decades, structural biology has shown how T-cell receptors engage peptide/major histocompatibility complex (MHC) complexes and provided insight into the mechanisms underlying antigen specificity and cross-reactivity. Here we review and contextualize our contributions, which have emphasized the influe...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2012.01165.x
更新日期：2012-11-01 00:00:00
abstract：:The monoclonal antibody, A2B4-2, specifically bound to and inhibited antigen-induced IL-2 release from the cloned pigeon cytochrome c-specific T cell hybrid, 2B4. The initial immunoprecipitation with these reagents demonstrated a protein of 85-90kd on non-reducing conditions, and two bands of 45-50 and 40-44 on reduci...
journal_title：Immunological reviews
pub_type： 杂志文章
doi：10.1111/j.1600-065x.1984.tb01107.x
更新日期：1984-10-01 00:00:00
abstract：:T cells are key players of the mammalian adaptive immune system. They experience different mechanical microenvironments during their life cycle, from the thymus, secondary lymph organs, and peripheral tissues that are free of externally applied force, but display variable substrate rigidities to the blood and lymphati...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12122
更新日期：2013-11-01 00:00:00
abstract：:Immunity results from a complex interplay between the antigen-non-specific innate immune system and the antigen-specific adaptive immune system. The cells and molecules of the innate system employ non-clonal recognition receptors including lectins, Toll-like receptors, NOD-like receptors, and helicases. B and T lympho...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2009.00884.x
更新日期：2010-03-01 00:00:00
abstract：:Innate lymphoid cells (ILC) are a recently identified group of innate lymphocytes that are preferentially located at barrier surfaces. Barrier surfaces are in direct contact with complex microbial ecosystems, collectively referred to as the microbiota. It is now believed that the interplay of the microbiota with host ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12580
更新日期：2017-09-01 00:00:00
abstract：:Lymphocytes can interfere with the activity of other lymphocytes in a thousand and one ways. A particular subset of so-called regulatory CD4+ T cells is capable of controlling the activity of other lymphocytes in yet another way. Their function is primarily defined by the ability to protect the integrity of tissues an...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.1820101.x
更新日期：2001-08-01 00:00:00
abstract：:The destiny of activated T cells is critical to the ultimate fate of immune response. After encountering antigen, naïve T cells receive signal 1 through the T-cell receptor (TCR)-major histocompatibility complex (MHC) plus antigenic peptide complex and signal 2 through "positive" costimulatory molecules leading to ful...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1046/j.1600-065x.2003.00088.x
更新日期：2003-12-01 00:00:00
abstract：:Human immunodeficiency virus infection is still one of the most important causes of morbidity and mortality in the world, with a disproportionate human and economic burden especially in poorer countries. Despite many years of intense research, an aspect that still is not well understood is what (immune) mechanisms con...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12691
更新日期：2018-09-01 00:00:00
abstract：:Major histocompatibility complex class II (MHCII) molecules drive the development, activation and homeostasis of CD4* T-helper cells. They play a central role in key processes of the adaptive immune system, such as the generation of T-cell-mediated immune responses, the regulation of antibody production and the develo...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2000.17813.x
更新日期：2000-12-01 00:00:00
abstract：:Almost four decades of research into the role of human leukocyte antigen-B27 (HLA-B27) in susceptibility to spondyloarthritis has yet to yield a convincing answer. New results from an HLA-B27 transgenic rat model now demonstrate quite convincingly that CD8(+) T cells are not required for the inflammatory phenotype. Di...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2009.00865.x
更新日期：2010-01-01 00:00:00
abstract：:Mice infected with Listeria monocytogenes (LM) generate protective CD8 cells of varying specificity. One subset, unlike conventional LM-immune CD8 cells, can respond to antigen-presenting cells (APC) treated with heat-killed LM (HKLM). These cells proved to have surprisingly uniform specificity, recognizing a product ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb00998.x
更新日期：1997-08-01 00:00:00
abstract：:Structures of two intact monoclonal antibodies were solved by X-ray diffraction analysis revealing, in both cases, the dispositions of all segments, as well as the structures of the hinge polypeptides. An IgG1, whose antigen is the drug phenobarbital, assumed a completely different conformation when compared with an I...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01186.x
更新日期：1998-06-01 00:00:00
abstract：:The common cytokine receptor gamma chain (gamma c) plays a critical role in lymphoid development through its participation in the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Absence of gamma c results in abnormal lymphopoiesis and immunodeficiency, as evidence by X-linked severe combined immunodeficiency (SCIDX1)...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1995.tb00091.x
更新日期：1995-12-01 00:00:00
abstract：:Vaccines need to be rationally designed in order be delivered to the immune system for maximizing induction of dynamic immune responses. Virus-like particles (VLPs) are ideal platforms for such 3D vaccines, as they allow the display of complex and native antigens in a highly repetitive form on their surface and can ea...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12863
更新日期：2020-07-01 00:00:00
abstract：:The general thrust of this volume is to review the roles of accessory cells in regulating T and B lymphocytes. To that end, we have summarized the evidence that indicates the crucial role that Langerhans cells play in the induction and expression of immunity to antigens that gain access to, or arise within, skin. Lang...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1990.tb00572.x
更新日期：1990-10-01 00:00:00
abstract：:The genes that encode molecules involved in antigen presentation within the class I and class II regions of the mammalian major histocompatibility complex (MHC) include several that are highly polymorphic. There is evidence that this polymorphism is maintained by positive selection, most likely overdominant selection,...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01381.x
更新日期：1999-02-01 00:00:00
abstract：:The age-associated changes in humoral immunity affect the quality more than the quantity of the antibody response. Changes in the quality of the antibody response with age include shifts in antibody specificities from foreign to autoantigens, in antibody isotypes from IgG to IgM, in antibody affinities from high to lo...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb01032.x
更新日期：1997-12-01 00:00:00
abstract：:Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Systems biology involves an iterative cycle, in which emerging biological problems drive the development of new technologies and computational tools. These technologies and ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00721.x
更新日期：2009-01-01 00:00:00
abstract：:Multiple myeloma (MM) is a tumor of long-lived bone marrow plasma cells (PCs). Nearly 40% of MM tumors have immunoglobulin H (IgH) translocations involving four recurrent chromosomal loci (oncogenes): 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (MMSET and FGFR3), and 16q23 (c-maf). Other MM tumors have Ig translocations...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2003.00052.x
更新日期：2003-08-01 00:00:00
