Differential contribution of Lck and Fyn protein tyrosine kinases to intraepithelial lymphocyte development.

Abstract:

:The developmental stages and the role of protein tyrosine kinases (PTK) in the maturation of CD3+CD8 alpha alpha+ intraepithelial lymphocytes (IEL) have not been extensively characterized. However, comparisons of thymic and extrathymic T cell development indicate that these processes involve some distinct signaling and selection events. We used mice deficient in Lck, Fyn, or both Lck and Fyn to analyze the role that these src-family PTK play in IEL development. In contrast to thymocyte development, we found that all IEL subsets develop in mice deficient for either kinase alone. However, lck-/- animals exhibited reduced numbers of TcR alphabeta+ CD8alpha alpha+ IEL, indicating that Lck is important in the development of these cells. Mice which lack both Lck and Fyn fail to generate TcR alphabeta+ IEL, suggesting that signaling through the preTcR, mediated by Lck and, to a lesser extent Fyn, is required for maturation of all TcR alphabeta+ IEL lineages. Interestingly, a small population of TcR gammadelta+ CD8 alpha alpha+ cells are apparent in lck-/-fyn-/- animals, demonstrating that TcR alphabeta+ CD8 alpha alpha+ and TcR gammadelta+ CD8alpha alpha+ IEL have distinct PTK requirements for their development or expansion. CD3-CD8alpha- CD44+ and CD3-CD8alpha alpha+ CD16/32+ B220+ cells comprise the majority of IEL in both lck-/- fyn-/- and rag -/- mice, while they are poorly represented in wildtype controls. Comparison of the cell surface phenotype of these putative precursor IEL in lck-/- fyn-/- and rag-/- animals suggests that IEL maturation in these animals is arrested at an equivalent developmental stage. Overall, the data presented demonstrate that signals mediated by Lck or Fyn direct TcR alphabeta+ CD8alpha alpha+ IEL maturation but are dispensable for the development of TcR gammadelta+ CD8 alpha alpha+ IEL.

journal_name

Eur J Immunol

authors

Page ST,van Oers NS,Perlmutter RM,Weiss A,Pullen AM

doi

10.1002/eji.1830270229

subject

Has Abstract

pub_date

1997-02-01 00:00:00

pages

554-62

issue

2

eissn

0014-2980

issn

1521-4141

journal_volume

27

pub_type

杂志文章
  • Functional CD1a is stabilized by exogenous lipids.

    abstract::Self-glycosphingolipids bind to surface CD1 molecules and are readily displaced by other CD1 ligands. This capacity to exchange antigens at the cell surface is not common to other antigen-presenting molecules and its physiological importance is unclear. Here we show that a large pool of cell-surface CD1a, but not CD1b...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200535544

    authors: Manolova V,Kistowska M,Paoletti S,Baltariu GM,Bausinger H,Hanau D,Mori L,De Libero G

    更新日期:2006-05-01 00:00:00

  • Genetic control of sensitivity to Moloney leukemia virus in mice. III. The three H-2 linked Rmv genes are immune response genes controlling the antiviral antibody response.

    abstract::It has been shown previously that three different H-2-associated genes control the resistance to viremia and leukemia in Moloney virus-infected mice: Rmv. 1, mapping to the I-A or less probably K regions; Rmv. 2, mapping to the I-C, S or G regions and Rmv. 3, mapping to the D or T regions. Experiments have been perfo...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830101205

    authors: Debré P,Boyer B,Gisselbrecht S,Bismuth A,Lévy JP

    更新日期:1980-12-01 00:00:00

  • Thymic stromal organization is regulated by the specificity of T cell receptor/major histocompatibility complex interactions.

    abstract::The thymic architecture is normally compartmentalized into a central medulla surrounded by a peripheral cortical region. We investigated how compartmentalization of the thymic stroma is regulated using T cell receptor (TCR)-transgenic mouse models. Our studies show that the signals generated by TCR/peptide/major histo...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830270121

    authors: Brabb T,Huseby ES,Morgan TM,Sant'Angelo DB,Kirchner J,Farr AG,Goverman J

    更新日期:1997-01-01 00:00:00

  • Stress protein (hsp73)-mediated, TAP-independent processing of endogenous, truncated SV40 large T antigen for Db-restricted peptide presentation.

    abstract::Transporter associated with antigen processing (TAP)-competent and TAP-deficient cell lines were transfected with expression plasmids encoding either the wild-type (wt) large tumor antigen (T-Ag) of SV40, or a truncated cytoplasmic variant (cT-Ag) of this viral protein. Stable expression of comparable levels of both f...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830270828

    authors: Schirmbeck R,Böhm W,Reimann J

    更新日期:1997-08-01 00:00:00

  • Specific binding of poly(I)-poly(C) to the membrane of murine B lymphocyte subsets.

    abstract::Indirect immunofluorescence revealed that 13% of BALB/c and 33% of CBA spleen cells of B type carry specific binding sites at their surface for double-stranded poly(I).poly(C). Pretreatment of BALB/c spleen cells with anti-mouse immunoglobulin serum increased the number of B cells capable of binding poly(I).poly(C) in...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830081213

    authors: Diamantstein T,Bittstein-Willinger E

    更新日期:1978-12-01 00:00:00

  • Human IgG subclass pattern of inducing complement-mediated cytolysis depends on antigen concentration and to a lesser extent on epitope patchiness, antibody affinity and complement concentration.

    abstract::The relative complement-mediated lytic capability of the IgG subclass isotypes was studied using a matched set of mouse-human chimeric anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies. The subclass pattern was shown to be highly dependent on variations in antigen concentration and to lesser extent on variation in ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830210103

    authors: Michaelsen TE,Garred P,Aase A

    更新日期:1991-01-01 00:00:00

  • Association of the p56lck protein tyrosine kinase with the Fc gamma RIIIA/CD16 complex in human natural killer cells.

    abstract::The multimeric Fc gamma RIIIA (CD16) complex is expressed on the surface of natural killer (NK) cells and is composed of a 50-70-kDa transmembrane glycoprotein Fc gamma receptor (CD16), the T cell receptor (TCR)-zeta chain, and the Fc epsilon RI gamma chain. Cross-linking Fc gamma RIIIA initiates the rapid tyrosine ph...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830231017

    authors: Cone JC,Lu Y,Trevillyan JM,Bjorndahl JM,Phillips CA

    更新日期:1993-10-01 00:00:00

  • The TLR-independent DNA recognition pathway in murine macrophages: Ligand features and molecular signature.

    abstract::Recognition of foreign DNA by cytosolic innate immune receptors triggers the production of IFN-beta. However, it is unclear whether different types of DNA ligands are recognized by similar receptors and whether the resulting response is distinct from the endosomal TLR response. To address these questions, we compared ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200939344

    authors: Karayel E,Bürckstümmer T,Bilban M,Dürnberger G,Weitzer S,Martinez J,Superti-Furga G

    更新日期:2009-07-01 00:00:00

  • A novel 90-kDa polypeptide (Tp90) possibly involved in an antigen-independent pathway of T cell activation.

    abstract::A novel surface molecule, Tp90, is described which appears to be involved in an antigen-independent pathway of human T lymphocyte activation. The Tp90 molecule was identified by a monoclonal antibody (mAb), MX20, obtained from a fusion using spleen cells of a mouse immunized with cells from two T cell leukemia lines, ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830170616

    authors: Carrel S,Salvi S,Giuffrè L,Isler P,Cerottini JC

    更新日期:1987-06-01 00:00:00

  • Cytolytic T cell hybridomas. II. Interleukin 2-independent cytolytic variants.

    abstract::Interleukin 2 (IL2)-dependent cytolytic hybrids usually loose IL2 dependence and cytolytic activity concomittantly. Here we describe an exceptional IL2-independent variant which lost IL2 receptor but retained cytolytic activity. When the IL2-independent cytolytic hybrid cells were fused with IL2-dependent cytolytic cl...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830150803

    authors: Haas W,Kisielow P

    更新日期:1985-08-01 00:00:00

  • xid mice fail to express an anti-dextran immune response but carry alpha(1-3)dextran-specific lymphocytes in their potential repertoire.

    abstract::Even after repeated immunizations with alpha(1-3)dextran (Dex) male (CBA/N x BALB/c)F1 mice fail to produce specific antibodies whereas nondefective female littermates express an idiotype-positive anti-Dex immune response. This failure of xid mice to express serum anti-Dex immunoglobulins is not only limited to immuni...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830181111

    authors: Selinka HC,Bösing-Schneider R

    更新日期:1988-11-01 00:00:00

  • The glycosylphosphatidylinositol-anchored CD59 protein stimulates both T cell receptor zeta/ZAP-70-dependent and -independent signaling pathways in T cells.

    abstract::The glycosylphosphatidylinositol (GPI)-anchored CD59 protein (human protectin) protects cells against complement-induced lysis, binds to CD2 and also transduces activation signals within T cells. We have further examined the biochemical signals transduced by CD59 and addressed its role in regard to the CD3-mediated si...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250704

    authors: Deckert M,Ticchioni M,Mari B,Mary D,Bernard A

    更新日期:1995-07-01 00:00:00

  • Thymic emigration: sphingosine-1-phosphate receptor-1-dependent models and beyond.

    abstract::The thymus is a primary lymphoid organ supporting the development of self-tolerant T cells. Key events in T-cell development in the thymus include lineage commitment, selection events, and thymic emigration. This review discusses the proposed role of sphingosine-1-phosphate and its receptors in the emigration of both ...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审

    doi:10.1002/eji.200838912

    authors: Drennan MB,Elewaut D,Hogquist KA

    更新日期:2009-04-01 00:00:00

  • IL-7 does not prevent pro-B/pre-B cell maturation to the immature/sIgM(+) stage.

    abstract::IL-7 plays many fundamental roles during murine B lineage development. One reported function is to maintain progenitors in a developmentally immature state by preventing differentiation to the surface IgM (sIgM)(+) stage. Withdrawal of IL-7 from cultures has been shown to lead to increases in mature traits such as RAG...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200425400

    authors: Milne CD,Fleming HE,Paige CJ

    更新日期:2004-10-01 00:00:00

  • IL-15 induces mast cell migration via a pertussis toxin-sensitive receptor.

    abstract::IL-15 induces proliferation, inhibits apoptosis and increases IL-4 production in murine mast cells. There is evidence that these activities are mediated via the uncharacterised receptor, IL-15R-X, rather than the classical three-chain IL-15 receptor. Effects of IL-15 on important aspects of mast cell biology, such as ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200526154

    authors: Jackson NE,Wang HW,Tedla N,McNeil HP,Geczy CL,Collins A,Grimm MC,Hampartzoumian T,Hunt JE

    更新日期:2005-08-01 00:00:00

  • Pyk2 is differentially regulated by beta1 integrin- and CD28-mediated co-stimulation in human CD4+ T lymphocytes.

    abstract::Beta1 integrins can provide T cell co-stimulation, but little is known concerning their downstream signaling pathways. We found that Pyk2, a focal adhesion kinase-related tyrosine kinase, is regulated by beta1 integrin signaling in human T cells. Stimulation of Jurkat T cells with the alpha4beta1 integrin ligand VCAM-...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199811)28:11<3867::AID-IMM

    authors: van Seventer GA,Mullen MM,van Seventer JM

    更新日期:1998-11-01 00:00:00

  • T cell activation by concanavalin A in the presence of cyclosporin A: immunosuppressor withdrawal induces NFATp translocation and interleukin-2 gene transcription.

    abstract::Cyclosporin A (CSA), an immunosuppressive agent used in organ transplantation and to treat some autoimmune diseases, blocks the Ca2+-dependent steps involved in T cell receptor triggering leading to interleukin (IL)-2 production. Considering that the early steps of T cell activation are insensitive to CSA, we asked wh...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260712

    authors: Bemer V,Truffa-Bachi P

    更新日期:1996-07-01 00:00:00

  • Differential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infection.

    abstract::IFN-gamma plays a crucial role in the defense against infection with Candida albicans. Since IL-18 and IL-12 are strong stimuli of IFN-gamma production, we investigated whether endogenous IL-18 and IL-12 are involved in the host defense during disseminated candidiasis. IL-18 knockout (IL-18-/-) mice, but not IL-12-/- ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200323737

    authors: Netea MG,Vonk AG,van den Hoven M,Verschueren I,Joosten LA,van Krieken JH,van den Berg WB,Van der Meer JW,Kullberg BJ

    更新日期:2003-12-01 00:00:00

  • Presentation of endogenous viral proteins in association with major histocompatibility complex class II: on the role of intracellular compartmentalization, invariant chain and the TAP transporter system.

    abstract::Major histocompatibility complex (MHC) class II-associated antigen presentation is mainly linked to processing of exogenous antigens upon cellular uptake by endocytosis, but has also been observed for endogenously synthesized antigens. We have studied the MHC class II-associated presentation of the endogenously synthe...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830251230

    authors: Oxenius A,Bachmann MF,Ashton-Rickardt PG,Tonegawa S,Zinkernagel RM,Hengartner H

    更新日期:1995-12-01 00:00:00

  • Neutrophil-active chemokines in in vivo imaging of neutrophil trafficking.

    abstract::Chemokines are proinflammatory mediators that regulate leukocyte trafficking at different steps of the leukocyte recruitment cascade. Studies using new imaging approaches and new mouse models are giving new insights into the role of chemokines in neutrophil migration at sites of inflammation. Conventional rolling and ...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审

    doi:10.1002/eji.201142231

    authors: Sanz MJ,Kubes P

    更新日期:2012-02-01 00:00:00

  • A pseudosymmetric cell adhesion regulatory domain in the beta7 tail of the integrin alpha4beta7 that interacts with focal adhesion kinase and src.

    abstract::The beta7 integrins alpha4beta7 and alphaEbeta7 play key roles in forming the gut-associated lymphoid tissue, and contribute to chronic inflammation. The alpha4beta7 integrin-mediated adhesion of activated lymphocytes is largely due to a transient increase in avidity from ligand-induced clustering of alpha4beta7 at th...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200535324

    authors: Krissansen GW,Singh J,Kanwar RK,Chan YC,Leung E,Lehnert KB,Kanwar JR,Yang Y

    更新日期:2006-08-01 00:00:00

  • Fine specificity of the H-2 linked immune response gene for the gallinaceous lysozymes.

    abstract::An immune response (Ir) gene is described which controls the ability of mice to respond to seven very closely related gallinaceous egg white lysozymes (GEL). This Ir-GEL gene locus is linked to the major histocompatibility locus of the mouse and operates at the level of the T cell. Responsiveness to the nonimmunogenic...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830050506

    authors: Hill SW,Sercarz EE

    更新日期:1975-05-01 00:00:00

  • Opposite effects of the synthetic immunomodulator, muramyl dipeptide, on rejection of mouse skin allografts.

    abstract::The influence of muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine) on the rejection of mouse skin allografts was investigated. While the 0.1-mg dose administered on days 7, 6, 5 prior to transplantation caused significant prolongation of the graft survival, the 0.5-mg dose administered on days 3, 2, 1 prior ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830131015

    authors: Zídek Z,Capková J,Boubelík M,Masek K

    更新日期:1983-10-01 00:00:00

  • Enforced expression of GATA3 allows differentiation of IL-17-producing cells, but constrains Th17-mediated pathology.

    abstract::The zinc-finger transcription factor GATA3 serves as a master regulator of T-helper-2 (Th2) differentiation by inducing expression of the Th2 cytokines IL-4, IL-5 and IL-13 and by suppressing Th1 development. Here, we investigated how GATA3 affects Th17 differentiation, using transgenic mice with enforced GATA3 expres...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200737840

    authors: van Hamburg JP,de Bruijn MJ,Ribeiro de Almeida C,van Zwam M,van Meurs M,de Haas E,Boon L,Samsom JN,Hendriks RW

    更新日期:2008-09-01 00:00:00

  • The peripheral T cell repertoire: independent homeostatic regulation of virgin and activated CD8+ T cell pools.

    abstract::Mature T cells may be produced in the thymus, or by expansion in the periphery. While thymus output of virgin cells ensures repertoire diversity, peripheral expansion increases the size of rare clones, and thus the efficiency of immune responses. We studied the role of both phenomena in the generation of the CD8+ T ce...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250802

    authors: Tanchot C,Rocha B

    更新日期:1995-08-01 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

  • Differences and similarities in the A2.1-restricted cytotoxic T cell repertoire in humans and human leukocyte antigen-transgenic mice.

    abstract::HLA-A2.1-binding peptides (n = 38) were screened for immunogenicity with human peripheral blood mononuclear cells in cytotoxic T lymphocyte (CTL) induction experiments in vitro and with splenocytes from HLA-A2.1/Kb transgenic mice following immunization in vivo. These data were compiled and analyzed to determine the l...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260115

    authors: Wentworth PA,Vitiello A,Sidney J,Keogh E,Chesnut RW,Grey H,Sette A

    更新日期:1996-01-01 00:00:00

  • Effects of human immunodeficiency virus type 1 on CD4 lymphocyte subset activation.

    abstract::The pathogenesis of the decline of CD4 lymphocyte counts accompanying the typical course of HIV-1 infection is not completely defined and might be related to a differential susceptibility of naive and memory cells to HIV-1 exposure. Here, we examined the effects induced by heat-inactivated HIV-1 virions on these lymph...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199906)29:06<1879::AID-IMM

    authors: Masci AM,Paz FL,Borriello A,Cassano S,Della Pietra V,Stoiber H,Matarese G,Della Ragione F,Zappacosta S,Racioppi L

    更新日期:1999-06-01 00:00:00

  • Selective expression of liver and activation-regulated chemokine (LARC) in intestinal epithelium in mice and humans.

    abstract::The liver and activation-regulated chemokine (LARC), also termed MIP-3alpha and Exodus, is a novel human CC chemokine with a selective chemotactic activity for lymphocytes and dendritic cells. Here we describe genomic and cDNA clones encoding the murine orthologue of LARC (mLARC). The gene consists of four exons and t...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199902)29:02<633::AID-IMMU

    authors: Tanaka Y,Imai T,Baba M,Ishikawa I,Uehira M,Nomiyama H,Yoshie O

    更新日期:1999-02-01 00:00:00

  • Differences between T helper cell type I (Th1) and Th2 cell lines in signalling pathways for induction of contact-dependent T cell help.

    abstract::B cells get help in the antibody response by presenting antigen to helper T (Th) cells. Upon antigen recognition, T cells produce lymphokines that act as growth and differentiation factors for B cells, but resting B cells require additional helper signals that depend on cell contact with an activated Th cell. Like lym...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830220114

    authors: Kawakami K,Parker DC

    更新日期:1992-01-01 00:00:00