Two-photon imaging of effector T-cell behavior: lessons from a tumor model.

Abstract:

:Recent advances in two-photon microscopy have provided a new way of visualizing the behavior of fluorescently tagged cells within their natural microenvironment. This technology has allowed for generating a detailed picture of the cellular interaction dynamics operant in the activation of T cells and B cells during primary immune responses within secondary lymphoid organs. In contrast, relatively little is known about the migratory and interactive behavior of effector T cells within peripheral organs. We have recently developed a two-photon microscopy model that enables tracking of cytotoxic T cells within tumors. We have demonstrated that tumor-infiltrating T lymphocytes (TILs) follow random migratory paths and that their migratory properties depend on signals from the T-cell receptor. We further showed that TILs underwent short- and long-term interactions with tumor cells as well as macrophages. Recently, we succeeded in dynamic imaging of the distribution of fluorescently tagged molecules within TILs at subcellular resolution, which will be instrumental for defining the composition of the lytic synapse as well as the targeted release of cytotoxic granules by these cells. The purpose of this review is to put our findings into the context of the current literature and to point out the molecular cues mediating effector T-cell function as candidates for future investigation.

journal_name

Immunol Rev

journal_title

Immunological reviews

authors

Ng LG,Mrass P,Kinjyo I,Reiner SL,Weninger W

doi

10.1111/j.1600-065X.2008.00596.x

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

147-62

eissn

0105-2896

issn

1600-065X

pii

IMR596

journal_volume

221

pub_type

杂志文章,评审
  • Shaping the repertoire of tumor-infiltrating effector and regulatory T cells.

    abstract::Many tumors express antigens that can be specifically or selectively recognized by T lymphocytes, suggesting that T-cell-mediated immunity may be harnessed for the immunotherapy of cancer. However, since tumors originate from normal cells and evolve within the context of self-tissues, the immune mechanisms that preven...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12166

    authors: Savage PA,Leventhal DS,Malchow S

    更新日期:2014-05-01 00:00:00

  • Negative regulation of lymphocyte development and function by the Cbl family of proteins.

    abstract::Negative regulation of intracellular signaling delivered by the antigen receptors and coreceptors plays an important role in lymphocyte development and activation. Recent data from our laboratory and others have identified the Cbl family of ubiquitin ligases as important negative regulators in both T-cell and B-cell a...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2008.00655.x

    authors: Huang F,Gu H

    更新日期:2008-08-01 00:00:00

  • Somatic hypermutation in normal and transformed human B cells.

    abstract::In the human, most IgM+IgD+ as well as CD5+ peripheral blood B cells express unmutated V genes and thus can be assigned to a pre-germinal centre (GC) stage of development. The memory B-cell compartment generated in the GC reaction and characterized by cells bearing somatically mutated V-region genes consists not only ...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065x.1998.tb01447.x

    authors: Klein U,Goossens T,Fischer M,Kanzler H,Braeuninger A,Rajewsky K,Küppers R

    更新日期:1998-04-01 00:00:00

  • Human Toll-like receptor-dependent induction of interferons in protective immunity to viruses.

    abstract::Five of the 10 human Toll-like receptors (TLRs) (TLR3, TLR4, TLR7, TLR8, and TLR9), and four of the 12 mouse TLRs (TLR3, TLR4, TLR7, TLR9) can trigger interferon (IFN)-alpha, IFN-beta, and IFN-lambda, which are critical for antiviral immunity. Moreover, TLR3, TLR7, TLR8, and TLR9 differ from TLR4 in two particularly i...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2007.00564.x

    authors: Zhang SY,Jouanguy E,Sancho-Shimizu V,von Bernuth H,Yang K,Abel L,Picard C,Puel A,Casanova JL

    更新日期:2007-12-01 00:00:00

  • Regulation of B cell activation and differentiation with factors generated by human T cell hybridomas.

    abstract::Human T cell hybridomas were generated by several techniques and the supernatants generated were screened for activity on human B cells. Three general activities were noted; B cell proliferation factor ( BCPF ), B cell differentiation factor (BCDF), and an IgA isotype-specific helper factor. BCPF acts on B cells to in...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065x.1984.tb00479.x

    authors: Mayer L,Fu SM,Kunkel HG

    更新日期:1984-04-01 00:00:00

  • The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets.

    abstract::Cancers are able to grow by subverting immune suppressive pathways, to prevent the malignant cells as being recognized as dangerous or foreign. This mechanism prevents the cancer from being eliminated by the immune system and allows disease to progress from a very early stage to a lethal state. Immunotherapies are new...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12528

    authors: Allard B,Longhi MS,Robson SC,Stagg J

    更新日期:2017-03-01 00:00:00

  • The high-affinity receptor for IgG, FcγRI, of humans and non-human primates.

    abstract::Non-human primate (NHP) models, especially involving macaques, are considered important models of human immunity and have been essential in preclinical testing for vaccines and therapeutics. Despite this, much less characterization of macaque Fc receptors has occurred compared to humans or mice. Much of the characteri...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12366

    authors: Chenoweth AM,Trist HM,Tan PS,Wines BD,Hogarth PM

    更新日期:2015-11-01 00:00:00

  • Cell circuits and niches controlling B cell development.

    abstract::Studies over the last decade uncovered overlapping niches for hematopoietic stem cells (HSCs), multipotent progenitor cells, common lymphoid progenitors, and early B cell progenitors. HSC and lymphoid niches are predominantly composed by mesenchymal progenitor cells (MPCs) and by a small subset of endothelial cells. N...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12749

    authors: Zehentmeier S,Pereira JP

    更新日期:2019-05-01 00:00:00

  • Dimer formation in immunoglobulin preparations and speculations on the mechanism of action of intravenous immune globulin in autoimmune diseases.

    abstract::IgG dimers occurring in therapeutic Ig preparations have been characterized as Id-anti-Id, in that the sites of interaction are localized to the distal tips of the Fab arms. The observation that such dimers are prevalent in Ig or Igi.v. prepared from large plasma pools, but absent in preparations from a single individ...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065x.1994.tb00861.x

    authors: Tankersley DL

    更新日期:1994-06-01 00:00:00

  • Innate immune recognition: mechanisms and pathways.

    abstract::The innate immune system is an evolutionarily ancient form of host defense found in most multicellular organisms. Inducible responses of the innate immune system are triggered upon pathogen recognition by a set of pattern recognition receptors. These receptors recognize conserved molecular patterns shared by large gro...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2000.917309.x

    authors: Medzhitov R,Janeway C Jr

    更新日期:2000-02-01 00:00:00

  • Somatic diversification of IgH genes in rabbit.

    abstract::Rabbits have helped elucidate one of the major immunologic puzzles, namely the genetic control of antibody diversity. The primary IgH antibody repertoire in rabbits is dominated by B cells that use the same germline VH-gene segment in VDJ gene rearrangements. The VDJ genes of essentially all B lymphocytes undergo soma...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065x.1998.tb01427.x

    authors: Knight KL,Barrington RA

    更新日期:1998-04-01 00:00:00

  • Cell biology and immunology of Leishmania.

    abstract::More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)- and Th2-dominated immune responses, respectively. This infectious disease model was later used to iden...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2010.00983.x

    authors: Mougneau E,Bihl F,Glaichenhaus N

    更新日期:2011-03-01 00:00:00

  • T follicular helper cell heterogeneity: Time, space, and function.

    abstract::T follicular helper (Tfh) cells play a crucial role in orchestrating the humoral arm of adaptive immune responses. Mature Tfh cells localize to follicles in secondary lymphoid organs (SLOs) where they provide help to B cells in germinal centers (GCs) to facilitate immunoglobulin affinity maturation, class-switch recom...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12740

    authors: Song W,Craft J

    更新日期:2019-03-01 00:00:00

  • The roles of Dok family adapters in immunoreceptor signaling.

    abstract::The mammalian Dok protein family has seven members (Dok-1-Dok-7). The Dok proteins share structural similarities characterized by the NH2-terminal pleckstrin homology and phosphotyrosine-binding domains followed by SH2 target motifs in the COOH-terminal moiety, indicating an adapter function. Indeed, Dok-1 was origina...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2009.00844.x

    authors: Mashima R,Hishida Y,Tezuka T,Yamanashi Y

    更新日期:2009-11-01 00:00:00

  • Inflammatory triggers of acute rejection of organ allografts.

    abstract::Solid organ transplantation is a vital therapy for end stage diseases. Decades of research have established that components of the adaptive immune system are critical for transplant rejection, but the role of the innate immune system in organ transplantation is just emerging. Accumulating evidence indicates that the i...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12146

    authors: Mori DN,Kreisel D,Fullerton JN,Gilroy DW,Goldstein DR

    更新日期:2014-03-01 00:00:00

  • Defects in the interferon-gamma and interleukin-12 pathways.

    abstract::The interferon-gamma (IFN-gamma)/interleukin-12 (IL-12) pathway is a pivotal player in the immune system and is central to controlling mycobacterial infections. We highlight the most recent and relevant advances in understanding this pathway and their repercussions on basic and clinical science. Human mutations in IFN...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.0105-2896.2005.00227.x

    authors: Rosenzweig SD,Holland SM

    更新日期:2005-02-01 00:00:00

  • B-cell homeostasis, competition, resources, and positive selection by self-antigens.

    abstract::In adult mice, the number of B lymphocytes remains constant under homeostatic control, in spite of the fact that B cells are produced continuously in numbers that largely exceed the number required to replenish the peripheral pools. It follows that each newly formed lymphocyte can only persist if another lymphocyte di...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.0105-2896.2004.0095.x

    authors: Gaudin E,Rosado M,Agenes F,McLean A,Freitas AA

    更新日期:2004-02-01 00:00:00

  • Neuroendocrine regulation of innate lymphoid cells.

    abstract::The activities of the immune system in repairing tissue injury and combating pathogens were long thought to be independent of the nervous system. However, a major regulatory role of immunomodulatory molecules released locally or systemically by the neuroendocrine system has recently emerged. A number of observations a...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12707

    authors: Quatrini L,Vivier E,Ugolini S

    更新日期:2018-11-01 00:00:00

  • Monocytes in the rat: phenotype and function during acute allograft rejection.

    abstract::Cells of the monocyte/macrophage system originate from the bone marrow, reach the organs via the blood, immigrate through postcapillary venules and further differentiate into organ-specific tissue macrophages. In rats and other species, activated monocytes/macrophages aggravate autoimmune reactions, rejection of non-v...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2001.1840104.x

    authors: Steiniger B,Stehling O,Scriba A,Grau V

    更新日期:2001-12-01 00:00:00

  • Death and Baxes: mechanisms of lymphotrophic cytokines.

    abstract::In this review, we briefly cover the critical requirements for interleukin-7 (IL-7) in thymocyte development and peripheral T-cell homeostasis. Part of the IL-7 effect is antiapoptotic or 'trophic' and we have studied the intracellular pathways involved in lymphocyte survival and death regulated by this cytokine. We r...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2003.00050.x

    authors: Khaled AR,Durum SK

    更新日期:2003-06-01 00:00:00

  • Molecular underpinning of B-cell anergy.

    abstract::A byproduct of the largely stochastic generation of a diverse B-cell specificity repertoire is production of cells that recognize autoantigens. Indeed, recent studies indicate that more than half of the primary repertoire consists of autoreactive B cells that must be silenced to prevent autoimmunity. While this silenc...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2010.00936.x

    authors: Yarkoni Y,Getahun A,Cambier JC

    更新日期:2010-09-01 00:00:00

  • T cells and follicular dendritic cells in germinal center B-cell formation and selection.

    abstract::Germinal centers (GCs) are specialized microenvironments formed after infection where activated B cells can mutate their B-cell receptors to undergo affinity maturation. A stringent process of selection allows high affinity, non-self-reactive B cells to become long-lived memory B cells and plasma cells. While the prec...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2010.00937.x

    authors: Vinuesa CG,Linterman MA,Goodnow CC,Randall KL

    更新日期:2010-09-01 00:00:00

  • Spatial and temporal coordination of antiviral responses by group 1 ILCs.

    abstract::Group 1 innate lymphocytes consist of a phenotypically, spatially, and functionally heterogeneous population of NK cells and ILC1s that are engaged during pathogen invasion. We are only beginning to understand the context-dependent roles that different subsets of group 1 innate lymphocytes play during homeostatic pert...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12710

    authors: Adams NM,Sun JC

    更新日期:2018-11-01 00:00:00

  • The role of innate immunity in Alzheimer's disease.

    abstract::The amyloid hypothesis has dominated Alzheimer's disease (AD) research for almost 30 years. This hypothesis hinges on the predominant clinical role of the amyloid beta (Aβ) peptide in propagating neurofibrillary tangles (NFTs) and eventual cognitive impairment in AD. Recent research in the AD field has identified the ...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12896

    authors: Ennerfelt HE,Lukens JR

    更新日期:2020-09-01 00:00:00

  • Variable expression of activation-linked surface antigens on human mast cells in health and disease.

    abstract::Mast cells (MC) are multipotent effector cells of the immune system. They contain an array of biologically active mediator substances in their granules. MC also express a number of functionally important cell surface antigens, including stem cell factor receptor (SCFR=kit=CD117), high affinity IgER (FcepsilonRI), or C...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2001.790108.x

    authors: Valent P,Schernthaner GH,Sperr WR,Fritsch G,Agis H,Willheim M,Bühring HJ,Orfao A,Escribano L

    更新日期:2001-02-01 00:00:00

  • Induction of allergic inflammation by interleukin-18 in experimental animal models.

    abstract::Interleukin-18 (IL-18) has been regarded as a proinflammatory cytokine because of its potent interferon-gamma-inducing activity. However, mutant mice that release excess amounts of IL-18 spontaneously develop pruritic chronic dermatitis-like atopic dermatitis (AD), suggesting the importance of IL-18 for the developmen...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.0105-2896.2004.00205.x

    authors: Tsutsui H,Yoshimoto T,Hayashi N,Mizutani H,Nakanishi K

    更新日期:2004-12-01 00:00:00

  • Chemokines in the systemic organization of immunity.

    abstract::Directed cellular migrations underlie immune system organization. Chemokines and their receptors (along with surface-adhesion molecules) are central to these migrations, targeting developing and mature leukocytes to tissues and microenvironments suitable for their differentiation and function. The chemokine CXCL12 and...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2003.00067.x

    authors: Campbell DJ,Kim CH,Butcher EC

    更新日期:2003-10-01 00:00:00

  • Fcγ receptors: genetic variation, function, and disease.

    abstract::Fcγ receptors (FcγRs) are key immune receptors responsible for the effective control of both humoral and innate immunity and are central to maintaining the balance between generating appropriate responses to infection and preventing autoimmunity. When this balance is lost, pathology results in increased susceptibility...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12341

    authors: Hargreaves CE,Rose-Zerilli MJ,Machado LR,Iriyama C,Hollox EJ,Cragg MS,Strefford JC

    更新日期:2015-11-01 00:00:00

  • Transdifferentiation and nuclear reprogramming in hematopoietic development and neoplasia.

    abstract::Cell transplantation and tissue regeneration studies indicate a surprisingly broad developmental potential for lineage-committed hematopoietic stem cells (HSCs). Under these conditions HSCs transition into myocytes, neurons, hepatocytes or other types of nonhematopoietic effector cells. Equally impressive is the progr...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2002.18703.x

    authors: French SW,Hoyer KK,Shen RR,Teitell MA

    更新日期:2002-09-01 00:00:00

  • Regulation of interleukin-12/interleukin-23 production and the T-helper 17 response in humans.

    abstract::Interleukin-12 (IL-12) and IL-23 share a common chain. Yet, their production in response to pathogens is differentially regulated, and their functions are distinct and often antithetic. IL-12 is involved in the induction or amplification of the T-helper (Th) type 1 response, whereas IL-23 has been associated with the ...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2008.00700.x

    authors: Lyakh L,Trinchieri G,Provezza L,Carra G,Gerosa F

    更新日期:2008-12-01 00:00:00