IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells.

Abstract:

:CD25(+)CD4(+) regulatory T cells inhibit the activation of autoreactive T cells in vitro and in vivo, and suppress organ-specific autoimmune diseases. The mechanism of CD25(+)CD4(+) T cells in the regulation of experimental autoimmune encephalomyelitis (EAE) is poorly understood. To assess the role of CD25(+)CD4(+) T cells in EAE, SJL mice were immunized with myelin proteolipid protein (PLP)(139-151) to develop EAE and were treated with anti-CD25 mAb. Treatment with anti-CD25 antibody following immunization resulted in a significant enhancement of EAE disease severity and mortality. There was increased inflammation in the central nervous system (CNS) of anti-CD25 mAb-treated mice. Anti-CD25 antibody treatment caused a decrease in the percentage of CD25(+)CD4(+) T cells in blood, peripheral lymph node (LN) and spleen associated with increased production of IFN-gamma and a decrease in IL-10 production by LN cells stimulated with PLP(130-151) in vitro. In addition, transfer of CD25(+)CD4(+) regulatory T cells from naive SJL mice decreased the severity of active EAE. In vitro, anti-CD3-stimulated CD25(+)CD4(+) T cells from naive SJL mice secreted IL-10 and IL-10 soluble receptor (sR) partially reversed the in vitro suppressive activity of CD25(+)CD4(+) T cells. CD25(+)CD4(+) T cells from IL-10-deficient mice were unable to suppress active EAE. These findings demonstrate that CD25(+)CD4(+) T cells suppress pathogenic autoreactive T cells in actively induced EAE and suggest they may play an important natural regulatory function in controlling CNS autoimmune disease through a mechanism that involves IL-10.

journal_name

Int Immunol

journal_title

International immunology

authors

Zhang X,Koldzic DN,Izikson L,Reddy J,Nazareno RF,Sakaguchi S,Kuchroo VK,Weiner HL

doi

10.1093/intimm/dxh029

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

249-56

issue

2

eissn

0953-8178

issn

1460-2377

journal_volume

16

pub_type

杂志文章
  • A high frequency of hybridomas from M54 mu heavy chain transgenic mice initially co-express transgenic and rearranged endogenous mu genes.

    abstract::The M54 transgenic mouse line, which carries the 17.2.25 Ig mu heavy chain gene, rearranges Ig heavy chains and expresses both transgenic and endogenous mu. B cell lineage development is selectively impaired in these mice and cells that simultaneously express transgenic and endogenous mu ('double-producers') are commo...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/5.9.1011

    authors: Lam KP,Herzenberg LA,Stall AM

    更新日期:1993-09-01 00:00:00

  • Role of alpha chain-IL-2 complex in the formation of the ternary complex of IL-2 and high-affinity IL-2 receptor.

    abstract::Using anti-Tac (anti-alpha chain) and 2R-B (anti-beta chain) antibodies, we studied the roles of IL-2 receptor subunits (alpha and beta chains) in the formation of IL-2 and high-affinity IL-2 receptor complex, which is the initial event of IL-2 induced T cell growth. High-affinity IL-2 binding which was undetectable i...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/2.6.521

    authors: Kamio M,Uchiyama T,Arima N,Itoh K,Ishikawa T,Hori T,Uchino H

    更新日期:1990-01-01 00:00:00

  • Differential expression of B7 co-stimulatory molecules by astrocytes correlates with T cell activation and cytokine production.

    abstract::Whether astrocytes utilize B7:CD28 co-stimulation to activate T cells mediating CNS inflammatory disease is controversial. In this report, primary astrocytes and murine astrocyte lines, generated by immortalization at two different times, day 7 or 45 of culture, were examined for their capability to express B7 co-stim...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/11.7.1169

    authors: Soos JM,Ashley TA,Morrow J,Patarroyo JC,Szente BE,Zamvil SS

    更新日期:1999-07-01 00:00:00

  • IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells.

    abstract::IL-18 is a proinflammatory cytokine that plays an important role in NK cell activation and T(h)1 response. IL-18 has a structural homology to IL-1, particularly IL-1beta. IL-18R, composed of IL-1R-related protein (IL-18Ralpha) and IL-1R accessory protein-like (IL-18Rbeta), belongs to the IL-1R family. Furthermore, IL-...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/12.2.151

    authors: Tominaga K,Yoshimoto T,Torigoe K,Kurimoto M,Matsui K,Hada T,Okamura H,Nakanishi K

    更新日期:2000-02-01 00:00:00

  • Heterogeneity within medullary-type TCRalphabeta(+)CD3(+)CD4(-)CD8(+) thymocytes in normal mouse thymus.

    abstract::The functional maturation process of medullary-type CD4(-)CD8(+) [CD8 single-positive (SP)] thymocytes remains largely uncharacterized. We describe a phenotypic analysis of CD8 SP medullary-type thymocytes and find a remarkable heterogeneity within this thymic cell population. While mature CD8(+) T cells in the periph...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/13.3.313

    authors: Tian T,Zhang J,Gao L,Qian XP,Chen WF

    更新日期:2001-03-01 00:00:00

  • HLA-DM and MHC class II molecules co-distribute with peptidase-containing lysosomal subcompartments.

    abstract::MHC class II molecules associate with peptides in the endocytic pathway. Different endosomal locations for peptide loading of class II molecules, varying from early endosomes (EE) to lysosomes, have been assigned on the basis of subcellular fractionation experiments. We have determined the intracellular location of HL...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/8.5.625

    authors: Fernandez-Borja M,Verwoerd D,Sanderson F,Aerts H,Trowsdale J,Tulp A,Neefjes J

    更新日期:1996-05-01 00:00:00

  • Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis.

    abstract::Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). She...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxv067

    authors: Goto K,Kaneko Y,Sato Y,Otsuka T,Yamamoto S,Goto S,Yamamoto K,Yamamoto T,Kawachi H,Madaio MP,Narita I

    更新日期:2016-04-01 00:00:00

  • TLR2-dependent recognition of Streptococcus suis is modulated by the presence of capsular polysaccharide which modifies macrophage responsiveness.

    abstract::Streptococcus suis capsular type 2 is an important swine pathogen and an agent of zoonosis. Although meningitis is the most common form of disease, septicemia and septic shock are also frequently reported. Despite reports that CD14 is involved in the recognition of encapsulated S. suis by host cells, the mechanisms un...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxm003

    authors: Graveline R,Segura M,Radzioch D,Gottschalk M

    更新日期:2007-04-01 00:00:00

  • Mechanisms that limit the diversity of antibody: three sequentially acting mechanisms that favor the spontaneous production of germline encoded anti-phosphatidyl choline.

    abstract::Antibody to phosphatidyl choline (PtC) is produced spontaneously in mice, by approximately 2-10% of naturally occurring CD5+ (B1) B cells in the peritoneum. Much of this antibody is encoded by the VH11 gene associated with a specific V kappa 9 gene. Constraints on the size and structure of the H chain CDR3 have been d...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/5.11.1365

    authors: Arnold LW,Spencer DH,Clarke SH,Haughton G

    更新日期:1993-11-01 00:00:00

  • Rag-1: a topoisomerase?

    abstract::Recombination activating genes Rag-1 and Rag-2 were isolated on the basis of their ability to confer V(D)J recombination activity when co-expressed in fibroblasts. The mode of action of the confer V(D)J recombination activity when co-expressed in fibroblasts. The mode of action of the products of these genes is not kn...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/5.2.231

    authors: Kallenbach S,Brinkmann T,Rougeon F

    更新日期:1993-02-01 00:00:00

  • Modulation of T cell homeostasis and alloreactivity under continuous FTY720 exposure.

    abstract::The immunomodulator FTY720 inhibits lymph node (LN) and thymic egress, thereby constraining T cell circulation and reducing peripheral T cell numbers. Here, we analyzed in mouse models the as yet scarcely characterized impact of long-term (up to 6 months) FTY720 exposure on T cell homeostasis and possible consequences...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxn023

    authors: Metzler B,Gfeller P,Wieczorek G,Li J,Nuesslein-Hildesheim B,Katopodis A,Mueller M,Brinkmann V

    更新日期:2008-05-01 00:00:00

  • Vaccination of the Leishmania major susceptible BALB/c mouse. I. The precise selection of peptide determinant influences CD4+ T cell subset expression.

    abstract::BALB/c mice are susceptible to cutaneous leishmaniasis upon infection with Leishmania major while C57BL/6 are not. There is a major promastigote surface protease (PSP or gp63) which is available in both native and recombinant forms, and for which the primary amino acid sequence is known. Immunization with PSP has been...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/6.5.785

    authors: Soares LR,Sercarz EE,Miller A

    更新日期:1994-05-01 00:00:00

  • Direct evidence for a functional role of HLA-DRB1 and -DRB3 gene products in the recognition of Dermatophagoides spp. (house dust mite) by helper T lymphocytes.

    abstract::The contribution of the HLA-DRB1, -B3, and -B5 gene products in the recognition of Dermatophagoides spp. (house dust mite) by helper T cells isolated from an atopic individual (HLA-DRw12, DR7; DRw52b) with perennial rhinitis was investigated. Using a panel of histocompatible and histoincompatible accessory cells, the ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/2.9.885

    authors: O'Hehir RE,Mach B,Berte C,Greenlaw R,Tiercy JM,Bal V,Lechler RI,Trowsdale J,Lamb JR

    更新日期:1990-01-01 00:00:00

  • Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells.

    abstract::Naturally arising CD25(+)CD4(+) regulatory T (T(R)) cells can be exploited to establish immunologic tolerance to non-self antigens. In vivo exposure of CD25(+)CD4(+) T cells from normal naive mice to alloantigen in a T cell-deficient environment elicited spontaneous expansion of alloantigen-specific CD25(+)CD4(+) T(R)...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh122

    authors: Nishimura E,Sakihama T,Setoguchi R,Tanaka K,Sakaguchi S

    更新日期:2004-08-01 00:00:00

  • Exposure of resting peripheral blood T cells to HIV-1 particles generates CD25+ killer cells in a small subset, leading to induction of apoptosis in bystander cells.

    abstract::Apoptosis is a major mechanism whereby HIV-1 depletes uninfected CD4+ and CD8+ T cells. We previously showed that resting peripheral blood T cells derived from healthy donors were killed by an apoptotic mechanism after adsorption to gp120-containing, protease-defective HIV-1 (L-2) particles, more effectively than pare...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/9.10.1453

    authors: Kameoka M,Suzuki S,Kimura T,Fujinaga K,Auwanit W,Luftig RB,Ikuta K

    更新日期:1997-10-01 00:00:00

  • Induction of ornithine decarboxylase activity in mouse B lymphocytes.

    abstract::We have examined the role in B cell activation of ornithine decarboxylase (ODC), the labile rate-limiting enzyme in the synthesis of polyamines thought to be required for S phase entry in all cells. When small resting mouse splenic B cells were stimulated with the mitogenic agents phorbol myristate acetate (PMA) plus ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/6.11.1777

    authors: Molitor J,Pace W,Stunz L,Vigna J,Louie S,Ashman R

    更新日期:1994-11-01 00:00:00

  • Modeling the presentation of C3d-coated antigen by B lymphocytes: enhancement by CR1/2-BCR co-ligation is selective for the co-ligating antigen.

    abstract::We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/14.3.241

    authors: Prechl J,Baiu DC,Horváth A,Erdei A

    更新日期:2002-03-01 00:00:00

  • Manipulation of EAT-2 expression promotes induction of multiple beneficial regulatory and effector functions of the human innate immune system as a novel immunomodulatory strategy.

    abstract::The signaling lymphocytic activation molecule (SLAM) receptor-associated adaptor Ewing's sarcoma-associated transcript-2 (EAT-2) is primarily expressed in innate immune cells including dendritic cells (DCs), macrophages and NK cells. A recent human HIV vaccine study confirmed that EAT-2 expression was associated with ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxt061

    authors: Aldhamen YA,Seregin SS,Aylsworth CF,Godbehere S,Amalfitano A

    更新日期:2014-05-01 00:00:00

  • Imaging CD8+ T cell dynamics in vivo using a transgenic luciferase reporter.

    abstract::After activation, populations of antigen-specific T cells flow between sites of antigen expression, local lymphoid structures and other lymphoid and non-lymphoid organs. In this study, we documented the in vivo dynamics of a CD8(+) T cell response to antigen delivered using herpes simplex virus amplicon vectors and re...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxm086

    authors: Azadniv M,Dugger K,Bowers WJ,Weaver C,Crispe IN

    更新日期:2007-10-01 00:00:00

  • Molecular basis of the synergistic production of IL-1 receptor antagonist by human neutrophils stimulated with IL-4 and IL-10.

    abstract::In this study, we report that the release of IL-1 receptor antagonist (IL-1ra) from IL-4-stimulated neutrophils is markedly enhanced in the presence of IL-10. We also show that up-regulation of IL-1ra release by IL-10 in IL-4-stimulated neutrophils takes place through IL-1ra mRNA stabilization and enhancement of IL-1r...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxf079

    authors: Crepaldi L,Silveri L,Calzetti F,Pinardi C,Cassatella MA

    更新日期:2002-10-01 00:00:00

  • Different cytoplasmic structure of the CD3 zeta family dimer modulates the activation signal and function of T cells.

    abstract::The TCR complex transduces the antigen recognition signal through common activation motifs present in both CD3 gamma delta epsilon chains and zeta dimers within the complex. We have investigated functional roles of the cytoplasmic domain in zeta and CD3 gamma delta epsilon for T cell activation in early and late respo...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/6.11.1671

    authors: Aoe T,Goto S,Ohno H,Saito T

    更新日期:1994-11-01 00:00:00

  • Selective IgG2 deficiency due to a point mutation causing abnormal splicing of the Cgamma2 gene.

    abstract::The mechanism underlying selective IgG subclass deficiency is largely unknown in humans. We have previously reported the acquisition of a complete IgG2 deficiency in a leukemia patient after bone marrow transplantation. Southern blot analysis showed a deletion including the Cgamma2 and Cgamma4 genes on one chromosome ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh192

    authors: Zhao Y,Pan-Hammarström Q,Zhao Z,Wen S,Hammarström L

    更新日期:2005-01-01 00:00:00

  • Modulation of CD4 co-receptor limits spontaneous autoimmunity when high-affinity transgenic TCR specific for self-antigen is expressed on a genetically resistant background.

    abstract::Myelin proteolipid protein (PLP) 139-151 is an immunodominant peptide that induces experimental autoimmune encephalomyelitis (EAE) in H-2(s) SJL/J mice. While PLP 139-151-specific TCR transgenic (tg) 4E3 mice develop fulminant spontaneous disease on the susceptible SJL/J background, spontaneous EAE is dramatically red...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxm094

    authors: Illés Z,Waldner H,Reddy J,Anderson AC,Sobel RA,Kuchroo VK

    更新日期:2007-10-01 00:00:00

  • Phenotype of B cells responding to the thymus-independent type-2 antigen polyvinyl pyrrolidinone.

    abstract::We have determined the origin and cell surface phenotype of B cells producing antibody in response to immunization with the non-self TI-2 antigen polyvinyl pyrrolidinone (PVP). We report that the responding cells are derived from precursors in adult bone marrow and display the phenotype characteristic of B-1 cells. By...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/8.4.533

    authors: Whitmore AC,Haughton G,Arnold LW

    更新日期:1996-04-01 00:00:00

  • NK-cell phenotype at interruption underlies widely divergent duration of CD4+-guided antiretroviral treatment interruption.

    abstract::Long-term side effects may represent a relevant burden of antiretroviral treatment (ART) in HIV-infected patients with good CD4 immune reconstitution over extended time spans. CD4-guided treatment interruption (TI) has been evaluated to address this point and may result in a wide spectrum of time off ART in different ...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxq462

    authors: Bozzano F,Nasi M,Bertoncelli L,Nemes E,Prati F,Marras F,Mussini C,Moretta L,Cossarizza A,De Maria A

    更新日期:2011-02-01 00:00:00

  • Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice.

    abstract::Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity. In the present study, we investigated the in vivo involvement of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) using Tyk2-deficient mice. Hind paws of wild-type mice showed massive s...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxr057

    authors: Ishizaki M,Muromoto R,Akimoto T,Ohshiro Y,Takahashi M,Sekine Y,Maeda H,Shimoda K,Oritani K,Matsuda T

    更新日期:2011-09-01 00:00:00

  • CD69 cell surface expression identifies developing thymocytes which audition for T cell antigen receptor-mediated positive selection.

    abstract::CD69, an 'activation marker' that is rapidly induced on mature T cells after stimulation through the T cell antigen receptor (TCR) was found to be expressed on approximately 10% of normal thymocytes. All of these CD69+ thymocytes express alpha beta TCR, and they include both TCRlowCD4+CD8+ and TCRhighCD4+CD8- or CD4-C...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/5.9.1139

    authors: Yamashita I,Nagata T,Tada T,Nakayama T

    更新日期:1993-09-01 00:00:00

  • Expression of I mu-C gamma hybrid germline transcripts subsequent to immunoglobulin heavy chain class switching.

    abstract::Germline CH transcripts initiate from a non-coding I exon and terminate downstream of the associated CH exons. Ig heavy chain class switch recombination from the VDJ-C mu gene to particular downstream CH genes appears to be regulated by a process that involves mitogen and/or cytokine induction of germline CH transcrip...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/6.4.491

    authors: Li SC,Rothman PB,Zhang J,Chan C,Hirsh D,Alt FW

    更新日期:1994-04-01 00:00:00

  • Induction of B cell apoptosis by co-cross-linking CD23 and sIg involves aberrant regulation of c-myc and is inhibited by bcl-2.

    abstract::A novel system to study the effects of co-cross-linking CD23/FceRII and sIg on murine B lymphocytes utilizes a highly multivalent form of anti-Ig prepared by covalently linking anti-Ig antibodies to a DNP-dextran backbone. CD23-sIg co-cross-linking is accomplished by the addition of DNP-specific monoclonal IgE. Previo...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/9.8.1131

    authors: Campbell KA,Studer EJ,Kilmon MA,Lees A,Finkelman F,Conrad DH

    更新日期:1997-08-01 00:00:00

  • Paradoxical alteration of acute-phase protein levels in patients with chronic hepatitis C treated with IFN-alpha2b.

    abstract::Previously we observed elevation of the serum concentration of two acute-phase protein (AFP) complement components (C9 and C1-inhibitor) in patients with chronic hepatitis C who responded (R) to IFN-alpha therapy, but not in non-responders (NR). In the present study we investigated the effect of high-dose IFN-alpha th...

    journal_title:International immunology

    pub_type: 杂志文章

    doi:10.1093/intimm/dxh024

    authors: Kalabay L,Nemesánszky E,Csepregi A,Pusztay M,Dávid K,Horváth G,Ibrányi E,Telegdy L,Pár A,Bíró A,Fekete B,Gervain J,Horányi M,Ribiczey P,Csöndes M,Kleiber M,Walentin S,Prohászka Z,Füst G

    更新日期:2004-01-01 00:00:00