Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice.

Abstract:

:Follicular helper T (Tfh) cells provide crucial help to germinal center B (GCB) cells for proper antibody production, and a specialized subset of regulatory T cells, follicular regulatory T (Tfr) cells, modulate this process. However, Tfr-cell function in the GC is not well understood. Here, we define Tfr cells as a CD4(+) Foxp3(+) CXCR5(hi) PD-1(hi) CD25(low) TIGIT(high) T-cell population. Furthermore, we have used a novel mouse model ("Bcl6FC") to delete the Bcl6 gene in Foxp3(+) T cells and thus specifically deplete Tfr cells. Following immunization, Bcl6FC mice develop normal Tfh- and GCB-cell populations. However, Bcl6FC mice produce altered antigen-specific antibody responses, with reduced titers of IgG and significantly increased IgA. Bcl6FC mice also developed IgG antibodies with significantly decreased avidity to antigen in an HIV-1 gp120 "prime-boost" vaccine model. In an autoimmune lupus model, we observed strongly elevated anti-DNA IgA titers in Bcl6FC mice. Additionally, Tfh cells from Bcl6FC mice consistently produce higher levels of Interferon-γ, IL-10 and IL-21. Loss of Tfr cells therefore leads to highly abnormal Tfh-cell and GCB-cell responses. Overall, our study has uncovered unique regulatory roles for Tfr cells in the GC response.

journal_name

Eur J Immunol

authors

Wu H,Chen Y,Liu H,Xu LL,Teuscher P,Wang S,Lu S,Dent AL

doi

10.1002/eji.201546094

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

1152-61

issue

5

eissn

0014-2980

issn

1521-4141

journal_volume

46

pub_type

杂志文章
  • Redirecting soluble antigen for MHC class I cross-presentation during phagocytosis.

    abstract::Peptides presented by MHC class I molecules are mostly derived from proteins synthesized by the antigen-presenting cell itself, while peptides presented by MHC class II molecules are predominantly from materials acquired by endocytosis. External antigens can also be presented by MHC class I molecules in a process refe...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201445156

    authors: Hari A,Ganguly A,Mu L,Davis SP,Stenner MD,Lam R,Munro F,Namet I,Alghamdi E,Fürstenhaupt T,Dong W,Detampel P,Shen LJ,Amrein MW,Yates RM,Shi Y

    更新日期:2015-02-01 00:00:00

  • T cell-specific gene targeting reveals that alpha4 is required for early T cell development.

    abstract::Alpha4-mediated signaling is involved in a variety of functions in mammalian cells. To determine whether this is true for immunocompetent cells, we generated mutant (Lck-alpha4-) mice in which the alpha4 gene was deleted in a T cell-specific manner using the Cre/loxP system. These mice showed impaired early T cell dev...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200323720

    authors: Hua DR,Inui S,Yamashita T,Maeda K,Takagi K,Takeda J,Sakaguchi N

    更新日期:2003-07-01 00:00:00

  • FTY720 enhances the activation-induced apoptosis of donor T cells and modulates graft-versus-host disease.

    abstract::FTY720 is a novel immunosuppressant that improves the outcomes after solid organ and bone marrow transplantation (BMT) due to the sequestration of T cells into LN. We tested the hypothesis that the sequestration of donor T cells in LN by FTY720 would enhance their interaction with host APC, thus causing a greater degr...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200636123

    authors: Hashimoto D,Asakura S,Matsuoka K,Sakoda Y,Koyama M,Aoyama K,Tanimoto M,Teshima T

    更新日期:2007-01-01 00:00:00

  • Commensal microflora and interferon-gamma promote steady-state interleukin-7 production in vivo.

    abstract::IL-7 is a major regulator of lymphocyte homeostasis; however, little is known about the mechanisms that regulate IL-7 production. To study Il7 gene regulation in vivo, we generated a novel IL-7-reporter mouse, which allows the non-invasive quantification of Il7 gene activity in live mice and, additionally, the simulta...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201040441

    authors: Shalapour S,Deiser K,Sercan O,Tuckermann J,Minnich K,Willimsky G,Blankenstein T,Hämmerling GJ,Arnold B,Schüler T

    更新日期:2010-09-01 00:00:00

  • Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/ADAM-17) involving a TIMP-3 dependent and independent mechanism.

    abstract::IL-10 is a potent anti-inflammatory molecule, which regulates TNF-alpha at multiple levels. We investigated whether IL-10 also modulated the activity of the TNF-alpha-converting enzyme (TACE). Using an ex vivo fluorogenic assay we observed that LPS rapidly induced TACE activity in monocytes coinciding with release of ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200737821

    authors: Brennan FM,Green P,Amjadi P,Robertshaw HJ,Alvarez-Iglesias M,Takata M

    更新日期:2008-04-01 00:00:00

  • Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands.

    abstract::Muramyl peptides are the building blocks of bacterial peptidoglycan, and their biological functions in mammals have been extensively studied. In particular, muramyl peptides trigger inflammation, contribute to host defense against microbial infections, and modulate the adaptive immune response to antigens. These bacte...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201040827

    authors: Magalhaes JG,Lee J,Geddes K,Rubino S,Philpott DJ,Girardin SE

    更新日期:2011-05-01 00:00:00

  • Monocytes induce E-selectin gene expression in endothelial cells: role of CD11/CD18 and extracellular matrix proteins.

    abstract::E-selectin is an endothelium-specific inducible adhesion molecule which binds several inflammatory cell types, including neutrophils, monocytes, natural killer cells and a subset of memory T cells. E-selectin is important in the initial rolling interaction of these cells on inflamed endothelium. The transient kinetics...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830261221

    authors: Noble KE,Panayiotidis P,Collins PW,Hoffbrand AV,Yong KL

    更新日期:1996-12-01 00:00:00

  • Frequency, heterogeneity and encephalitogenicity of T cells specific for myelin oligodendrocyte glycoprotein in naive outbred primates.

    abstract::Auto-reactive T cells present in healthy subjects remain in a state of unresponsiveness, but may trigger autoimmunity under various situations. Although myelin oligodendrocyte glycoprotein (MOG) is a potential target antigen in multiple sclerosis (MS), MOG-reactive T cell responses are present in the blood of both hea...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(2001010)31:10<2942::aid-immu2942

    authors: Villoslada P,Abel K,Heald N,Goertsches R,Hauser SL,Genain CP

    更新日期:2001-10-01 00:00:00

  • Regional sublocalization of the human CD69 gene to chromosome bands 12p12.3-p13.2, the predicted region of the human natural killer cell gene complex.

    abstract::The early activation antigen CD69 is a member of a supergene family of type II integral membrane proteins with a C-type lectin domain. In recent reports the genes encoding the natural killer (NK) cell-related molecules of this supergene family, NKR-P1, NK1.1 and Ly-49, were shown to be clustered in a chromosomal regio...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830231051

    authors: Schnittger S,Hamann J,Dannenberg C,Fiebig H,Strauss M,Fonatsch C

    更新日期:1993-10-01 00:00:00

  • Allotype suppression in the chicken. III. Analysis of the recovery form suppression by neonatally injected or maternal antibodies.

    abstract::Injection of M-1 (Cmu), G-1 (Cgamma) heterozygous chickens on the day of hatch with anti-IgM-1 antiserum induced allotype suppression from which chickens recovered over a period of approximately 4 months. The suppression of the serum IgM-1 levels was matched by a decrease in the number of splenic and peripheral blood ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830110407

    authors: Ratcliffe MJ,Ivanyi J

    更新日期:1981-04-01 00:00:00

  • NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells.

    abstract::NKp46 is a novel triggering receptor expressed by all human NK cells that is involved in natural cytotoxicity. In this study we show that the surface density of NKp46 may vary in different NK cells and that a precise correlation exists between the NKp46 phenotype of NK clones and their natural cytotoxicity against HLA...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199905)29:05<1656::AID-IMM

    authors: Sivori S,Pende D,Bottino C,Marcenaro E,Pessino A,Biassoni R,Moretta L,Moretta A

    更新日期:1999-05-01 00:00:00

  • Loss of interleukin 2 dependence in cloned interleukin 2-dependent rat T lymphocyte x BW5147 hybridomas is not associated with segregation of a specific pair of rat chromosomes.

    abstract::A fusion between the mouse AKR thymoma BW5147 and a culture of homogeneously OX8+ (CD8) rat T lymphoblasts yield interleukin (IL) 2-dependent T cell hybridomas when selected in HAT medium supplemented with IL 2-containing supernatants of concanvalin A-activated cells and dexamethasone. IL 2-independent variants can be...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190704

    authors: Somoza C,Fernández-Ruiz E,Jotterand-Bellomo M,Sanz E,Nabholz M,Silva A

    更新日期:1989-07-01 00:00:00

  • Receptors for immune complexes on cells within a polyoma virus-induced murine sarcoma.

    abstract::Cells present in the polyoma virus-induced murine ascites tumor SEYF-a showed the capacity to fix soluble immune complexes of ovalbumin anti-ovalbumin. The fixation could be inhibited by preincubating the cells with antisera directed against H-2 antigens and with syngeneic anti-tumor antibodies. The latter did not rea...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830060810

    authors: Braslawsky GR,Serban D,Witz IP

    更新日期:1976-08-01 00:00:00

  • Presence of CD8 alpha-CD8 beta-positive TcR gamma/delta thymocytes in the fetal murine thymus and their in vitro expansion with interleukin-7.

    abstract::Several groups have described that a low percentage of in vitro cultured T cell receptor (TcR) gamma/delta cells express CD8. Contrary to TcR alpha/beta cells, however, CD8 on these TcR gamma/delta cells was shown to be a CD8 alpha homodimer. We describe here that addition of interleukin-7 (IL-7) to a short-term in vi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830220902

    authors: Leclercq G,De Smedt M,Plum J

    更新日期:1992-09-01 00:00:00

  • Towards an idiotype vaccine against mammary tumors. Induction of an immune response to breast cancer-associated antigens by anti-idiotypic antibodies.

    abstract::Previously we have reported on the production of two sets of human monoclonal antibodies reacting with mouse mammary tumor virus (MMTV) and human mammary tumor virus (HuMTV) cross-reacting antigens. B11 is a monoclonal IgG generated by the human-human hybridoma technique using axillary lymph node of breast cancer pati...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830181109

    authors: Smorodinsky NI,Ghendler Y,Bakimer R,Chaitchuk S,Keydar I,Shoenfeld Y

    更新日期:1988-11-01 00:00:00

  • Comparative study of VH gene family usage by newborn xid and non-xid mice, newborn NZB and adult NZB mice, and by splenic and peritoneal cavity B cell compartments.

    abstract::RNA from 170 different Ig-secreting hybridomas was hybridized with VH gene probes 7183, QUPC52, S107, J558, J606, 36-60, V31, X-24 and V-GAM 3.8, with the aim of comparing xid to non-xid mice, neonatal NZB to adult NZB, and the peritoneal cavity with the splenic compartments for VH gene family expression. Our results ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830181217

    authors: Dighiero G,Lim A,Lembezat MP,Kaushik A,Andrade L,Freitas A

    更新日期:1988-12-01 00:00:00

  • CD8+ T-cell cross-competition is governed by peptide-MHC class I stability.

    abstract::A major contributing factor to the final magnitude and breadth of CD8(+) T-cell responses to complex antigens is immunodomination, where CD8(+) T cells recognizing their cognate ligand inhibit the proliferation of other CD8(+) T cells engaged with the same APC. In this study, we examined how the half-life of cell s...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201142010

    authors: Galea I,Stasakova J,Dunscombe MS,Ottensmeier CH,Elliott T,Thirdborough SM

    更新日期:2012-01-01 00:00:00

  • Trypanosome-induced suppression of anti-parasite responses during experimental African trypanosomiasis.

    abstract::The effect of Trypanosoma brucei infections on parasite-specific antibody responses was examined by immunization of infected mice with radio-attenuated trypanosomes of a noncross-reacting clone. Antibody titers (total Ig) against variant surface antigen were determined by indirect immunofluorescence. The suppression r...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830101216

    authors: Sacks DL,Askonas BA

    更新日期:1980-12-01 00:00:00

  • Genetic and functional characterization of an antiserum to the lipid A-specific triggering receptor on murine B lymphocytes.

    abstract::The inheritance of responsiveness to lipopolysaccharide (LPS), and of a marker recognized in LPS-reactive cells by a heterologous antiserum, was studied in crosses between C3H/HeJ (nonresponder) and C3H/Tif (high responder) mice. F1 hybrid mice show codominant expression of these traits: (a) LPS-reactive cells are onl...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830080113

    authors: Coutinho A,Forni L,Watanabe T

    更新日期:1978-01-01 00:00:00

  • A synthetic HIV-1 Tat protein breaches the skin barrier and elicits Tat-neutralizing antibodies and cellular immunity.

    abstract::The HIV-1 Tat protein plays a critical role in the pathogenesis of HIV and has been considered as a candidate vaccine antigen. In an effort to design a non-invasive vaccination strategy against HIV-1 that stimulates the induction of systemic and mucosal immune responses, we studied the transcutaneous delivery of a syn...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200425313

    authors: Partidos CD,Moreau E,Chaloin O,Tunis M,Briand JP,Desgranges C,Muller S

    更新日期:2004-12-01 00:00:00

  • Vitamin A notches up CD11b hi DC development.

    abstract::Vitamin A and its metabolite retinoic acid influence various aspects of immunity. Although the capacity of vitamin A to condition intestinal CD103(+) DCs to imprint tissue-specific homing programs onto activated lymphocytes is well documented, it is unclear whether vitamin A also regulates DC populations in other tiss...

    journal_title:European journal of immunology

    pub_type: 评论,杂志文章

    doi:10.1002/eji.201343631

    authors: Stock AT,Bedoui S

    更新日期:2013-06-01 00:00:00

  • A novel human HER2-derived peptide homologous to the mouse K(d)-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals.

    abstract::A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K(d)-restricted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor rejection antigen in an in vivo assay. Since the anchor motif of mouse K(d) for peptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200011)30:11<3338::AID-IMMU3338>

    authors: Okugawa T,Ikuta Y,Takahashi Y,Obata H,Tanida K,Watanabe M,Imai S,Furugen R,Nagata Y,Toyoda N,Shiku H

    更新日期:2000-11-01 00:00:00

  • Effect of protein A and its fragment B on the catabolic and Fc receptor sites of IgG.

    abstract::Radiolabeled protein A from Staphylococcus aureus (SpA) injected i.v. into mice and rabbits forms a soluble [(IgG)2-(SpA)1]2 complex (Mr = 684 000) which is identical in composition to that formed by SpA in vitro with an equivalent amount or an excess of IgG. A soluble rabbit IgG-SpA complex injected into a mice or ra...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830130802

    authors: Dima S,Medeşan C,Moţa G,Moraru I,Sjöquist J,Gheţie V

    更新日期:1983-08-01 00:00:00

  • Differences in effect of isoproterenol stimulation on levels of cyclic AMP in human B and T lymphocytes.

    abstract::The level of cyclic AMP (cAMP) in human lymphocytes in the presence or absence of isoproterenol stimulation was studied in various lymphocyte subpopulations containing different proportions of B and T lymphocytes. Lymphocytes from thymus and peripheral blood (which contain a majority of T cells) were more sensitive to...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830061117

    authors: Niaudet P,Beaurain G,Bach MA

    更新日期:1976-11-01 00:00:00

  • Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II.

    abstract::The viral CC chemokine macrophage inhibitory protein-II (vMIP-II) encoded by human herpes virus 8 (HHV-8) binds to multiple chemokine receptors, however, its ability to control the initial recruitment of specific leukocyte subtypes from the peripheral circulation has not been fully clarified. Here we show that vMIP-II...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200108)31:8<2458::aid-immu24

    authors: Weber KS,Gröne HJ,Röcken M,Klier C,Gu S,Wank R,Proudfoot AE,Nelson PJ,Weber C

    更新日期:2001-08-01 00:00:00

  • Signaling through CD19, Fc receptors or transforming growth factor-beta: each inhibits the activation of resting human B cells differently.

    abstract::To understand further the roles that negative regulatory signals may play in B cell immune responses, we compared three inhibitors of B cell proliferation: cross-linking CD19 with monoclonal antibody (mAb), signaling through Fc receptors by intact anti-mu mAb, and transforming growth factor-beta (TGF-beta). Each agent...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830200516

    authors: Barrett TB,Shu GL,Draves KE,Pezzutto A,Clark EA

    更新日期:1990-05-01 00:00:00

  • Massive inflammatory syndrome and lymphocytic immunodeficiency in KARAP/DAP12-transgenic mice.

    abstract::KARAP/DAP12 is a broadly distributed transmembrane signaling polypeptide with an immunoreceptor tyrosine-based activation motif, and is non-covalently associated with a variety of activating surface receptors. We report here the characterization of transgenic mice that overexpress KARAP/DAP12 polypeptides in both myel...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200209)32:9<2653::AID-IMMU2653>3

    authors: Lucas M,Daniel L,Tomasello E,Guia S,Horschowski N,Aoki N,Figarella-Branger D,Gomez S,Vivier E

    更新日期:2002-09-01 00:00:00

  • Inhibition of CD1d1-mediated antigen presentation by the vaccinia virus B1R and H5R molecules.

    abstract::Vaccinia virus (VV) has been most commonly used as the vaccine to protect individuals against the causative agent of smallpox (variola virus), but it also uses a number of strategies meant to evade or blunt the host's antiviral immune response. Natural killer T (NKT) cells are a subset of immunoregulatory CD1d-restric...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200636024

    authors: Webb TJ,Litavecz RA,Khan MA,Du W,Gervay-Hague J,Renukaradhya GJ,Brutkiewicz RR

    更新日期:2006-10-01 00:00:00

  • IFN-alpha-mediated increase in cytolytic activity of maturing NK cell upon exposure to HSV-infected myelomonocytes.

    abstract::Impaired control of chronic pathogen replication may be associated to alterations of NK-cell function. Whether mechanisms underlying this dysfunction involve perturbations of differentiating NK cells is still unknown. We studied an "in vitro" model of differentiation from CD34(+)Lin(-) precursors growing only myelomon...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200838532

    authors: Costa P,Sivori S,Bozzano F,Martini I,Moretta A,Moretta L,De Maria A

    更新日期:2009-01-01 00:00:00

  • CD4+8- help prevents rapid deletion of CD8+ cells after a transient response to antigen.

    abstract::We have followed the fate of mature CD8+ T cells with a male-specific transgenic T cell receptor after antigenic stimulation with hemopoietic cells in the absence or presence of help. Our data show that mature CD8+ T cells can be deleted after a 3-week period of transient activation and that help, e.g. in the form of ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830230835

    authors: Kirberg J,Bruno L,von Boehmer H

    更新日期:1993-08-01 00:00:00