Andrew J. Caton

The Wistar Institute

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Meenhard Herlyn

The Wistar Institute

Zhaoyuan Hou

Tongren Hospital

Jan Erikson

The Wistar Institute

Frank J. Rauscher

The Wistar Institute

Electron Kebebew

Stanford Medicine

Bruce Malkowicz

University of Pennsylvania

Hongzhuang Peng

Southwest Medical University

William J. Fredericks

United Aircraft (Russia)

Qihong Huang

Shandong University

Jeremy W. Prokop

Corewell Health

Cooperative Institutions

Microsoft (Brazil)

125

New Valve Technology (Germany)

123

University of New Orleans

122

University of Pennsylvania

107

The Wistar Institute

Harvard University

National Institutes of Health

Hospital of the University of Pennsylvania

Massachusetts General Hospital

University of Alabama at Birmingham

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Supplementary Table S1 from LIMD2 Is a Small LIM-Only Protein Overexpressed in Metastatic Lesions That Regulates Cell Motility and Tumor Progression by Directly Binding to and Activating the Integrin-Linked Kinase

Hongzhuang Peng Mehdi Talebzadeh-Farrooji Michael Osborne Jeremy W. Prokop Paul C. McDonald

<p>Data collection and refinement statistics for the LIMD2 protein.</p>

Integrin-linked kinase

10.1158/0008-5472.22401207

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Citations (0)

Inducible MHC Class II Expression by Mast Cells Supports Effector and Regulatory T Cell Activation

The Journal of Immunology (2009)

Taku Kambayashi Eric J. Allenspach John T. Chang Tao Zou Jonathan E. Shoag

In addition to their well-established role as regulators of allergic response, recent evidence supports a role for mast cells in influencing the outcome of physiologic and pathologic T cell responses. One mechanism by which mast cells (MCs) influence T cell function is indirectly through secretion of various cytokines. It remains unclear, however, whether MCs can directly activate T cells through Ag presentation, as the expression of MHC class II by MCs has been controversial. In this report, we demonstrate that in vitro stimulation of mouse MCs with LPS and IFN-gamma induces the expression of MHC class II and costimulatory molecules. Although freshly isolated peritoneal MCs do not express MHC class II, an in vivo inflammatory stimulus increases the number of MHC class II-positive MCs in situ. Expression of MHC class II granted MCs the ability to process and present Ags directly to T cells with preferential expansion of Ag-specific regulatory T cells over naive T cells. These data support the notion that, in the appropriate setting, MCs may regulate T cell responses through the direct presentation of Ag.

10.4049/jimmunol.0803180

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Citations (143)

The Regulation and Activation Potential of Autoreactive B Cells

Immunologic Research (2003)

Michele L. Fields Su-jean Seo Simone A. Nish Jeff H. Tsai Andrew J. Caton

B-1 cell

10.1385/ir:27:2-3:219

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Citations (13)

Anergy and suppression regulate CD4+ T cell responses to a self peptide

European Journal of Immunology (2000)

Martha S. Jordan Michael P. Riley Harald von Boehmer Andrew J. Caton

To examine the role of cognate peptide in establishing CD4+ T cell tolerance, we have mated transgenic mice that express the major I-Ed-restricted determinant (S1) from the influenza virus PR8 hemagglutinin (HA28 mice) with mice expressing a S1-specific T cell receptor (TS1 mice). Surprisingly, S1-specific CD4+ T cells were not substantially deleted in TS1xHA28 mice; indeed, lymph node cells expressing the S1-specific TCR were as abundant in TS1xHA28 mice as in TS1 mice. The S1-specific T cells in TS1xHA28 mice were, however, impaired in their ability to respond to S1 peptide both in vitro and in vivo, and contained two distinct populations. Approximately half expressed a unique cell surface phenotype (CD25hi / CD45RBint) and had been anergized by the neo-self S1 peptide. The remainder responded normally to the S1 peptide if purified away from the anergic T cells, but their proliferation was suppressed when the anergic T cells were also present in unfractionated lymphnode cells or in mixed cultures. These findings establish that anergy and suppression are coordinated mechanisms by which autoreactive CD4+ T cells are regulated and that anergic / suppressor CD4+ T cells can develop in response to self peptides.

Clonal anergy

10.1002/1521-4141(200001)30:1<136::aid-immu136>3.0.co;2-0

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Citations (115)

CD4+ CD25+ Regulatory T Cell Repertoire Formation in Response to Varying Expression of a neo-Self-Antigen

The Journal of Immunology (2004)

Melissa A. Lerman Joseph Larkin Cristina Cozzo Martha S. Jordan Andrew J. Caton

Abstract We have examined the development of self-peptide-specific CD4+CD25+ regulatory T cells in lineages of transgenic mice that express the influenza virus PR8 hemagglutinin (HA) under the control of several different promoters (HA transgenic mice). By mating these lineages with TS1-transgenic mice expressing a TCR that recognizes the major I-Ed-restricted determinant from HA (site 1 (S1)), we show that S1-specific T cells undergo selection to become CD4+CD25+ regulatory T cells in each of the lineages, although in varying numbers. In some lineages, S1-specific CD4+CD25+ regulatory T cells are highly abundant; indeed, TS1xHA-transgenic mice can contain as many S1-specific CD4+ T cells as are present in TS1 mice, which do not express the neo-self HA. In another lineage, however, S1-specific thymocytes are subjected to more extensive deletion and far fewer S1-specific CD4+CD25+ regulatory T cells accumulate in the periphery. We show that radioresistant stromal cells can direct both deletion and CD4+CD25+ regulatory T cell selection of S1-specific thymocytes. Interestingly, even though their numbers can vary, the S1-specific CD4+CD25+ regulatory T cells in all cases coexist with clonally related CD4+CD25− T cells that lack regulatory function. These findings show that the formation of the CD4+CD25+ regulatory T cell repertoire is sensitive to variations in the expression of self-peptides.

Regulatory T cell

10.4049/jimmunol.173.1.236

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Citations (76)

Antibody-Induced Transplantation Tolerance That Is Dependent on Thymus-Derived Regulatory T Cells

The Journal of Immunology (2006)

Shaoping Deng Daniel J. Moore Xiaolun Huang Muhammad M. Mohiuddin Major K. Lee

Targeting of the CD45RB isoform by mAb (anti-CD45RB) effectively induces donor-specific tolerance to allografts. The immunological mechanisms underlying the tolerant state remain unclear although some studies have suggested the involvement of regulatory T cells (T-regs). Although their generative pathway remains undefined, tolerance promoting T-regs induced by systemic anti-CD45RB treatment have been assumed to originate in the peripheral immune system. We demonstrate herein that separable effects on the peripheral and central immune compartments mediate graft survival induced by anti-CD45RB administration. In the absence of the thymus, anti-CD45RB therapy is not tolerogenic though it retains peripheral immunosuppressive activity. The thymus is required for anti-CD45RB to produce indefinite graft survival and donor-specific tolerance, and this effect is accomplished through thymic production of donor-specific T-regs. These data reveal for the first time an Ab-based tolerance regimen that relies on the central tolerance pathway.

Peripheral tolerance

Central tolerance

10.4049/jimmunol.176.5.2799

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Citations (32)

Specialized CC-chemokine secretion by Th1 cells in destructive autoimmune myocarditis

Journal of Autoimmunity (2003)

Howard K. Song Hooman Noorchashm Tina H. Lin Daniel J. Moore Siri Atma W. Greeley

CCL5

10.1016/s0896-8411(03)00110-0

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Citations (18)

Abstract 5219: The LIM protein LIMD2 functions as an effector and biomarker for metastasis in multiple tumor types

Cancer Research (2011)

Hongzhuang Peng Zhaoyuan Hou Mei He Electron Kebebew Torben F. Ørntoft

Abstract The LIM domain is found in proteins from a wide variety of eukaryotic organisms. The LIM domain is organized as a tandem zinc-finger structure that functions as a modular protein-binding interface. LIM domain containing proteins have diverse cellular roles such as regulators of gene expression, cytoarchitecture, cell adhesion, cell motility, signal transduction, and biosensors. LIMD2 belongs to the LIM only family of LIM proteins and was identified as a biomarker for papillary thyroid carcinoma lymph node metastasis from molecular profiling of matched samples. However, the biological function of LIMD2 remains unknown. To identify whether LIMD2 is a biomarker for other cancers, highly specific LIMD2 polyclonal and monoclonal antibodies were developed and several cancer cell lines were tested for LIMD2 expression. These cancer cell lines were derived from breast cancer, melanoma, bladder cancer, and thyroid cancer. We found that the cancer cell lines derived from more aggressive tumors exhibited higher levels of LIMD2 protein expression. Furthermore, cells expressing higher levels of LIMD2 had increased migratory capabilities. Over-expression of LIMD2 protein in the less aggressive bladder cancer cell line (RT4) showed an increase in migration and colony formation ability. Conversely, knockdown of LIMD2 using siRNA decreased the migratory ability of the malignant melanoma cancer cell line and caused morphological changes in these cells. These data not only underscore the importance of LIMD2 as a key metastatic biomarker, but also suggest that LIMD2 may play a functional role in tumorgenicity. LIMD2 may also serve as a novel anti-metastatic target to improve the efficacy of conventional cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5219. doi:10.1158/1538-7445.AM2011-5219

10.1158/1538-7445.am2011-5219

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Virus-Induced Maturation and Activation of Autoreactive Memory B Cells

The Journal of Experimental Medicine (2000)

Amy J. Reed Michael P. Riley Andrew J. Caton

We have examined B cell populations that participate in distinct phases of the immune response to the influenza virus A/PR/8/34 hemagglutinin (HA) for their susceptibility to negative selection in mice that express the HA as a neo-self-antigen (HA104 mice). We demonstrated previously that specificity for the neo-self-HA causes a population of immunoglobulin G antibody-secreting cells, which dominate the primary response to virus immunization in BALB/c mice, to be negatively selected in HA104 mice. We find here that in contrast to these primary response B cells, HA-specific memory response B cells developed equivalently in HA104 and nontransgenic (BALB/c) mice. Indeed, there was no indication that HA-specific B cells were negatively selected during memory formation in influenza virus-immunized HA104 mice, even though the neo-self-HA can be recognized by memory B cells. Furthermore, HA-specific autoantibodies were induced in the absence of virus immunization by mating HA104 mice with mice transgenic for a CD4(+) HA-specific T cell receptor. These findings indicate that specificity for a self-antigen does not prevent the maturation of autoreactive B cells in the germinal center pathway. Rather, the availability of CD4(+) T cell help may play a crucial role in regulating autoantibody responses to the HA in HA104 mice.

Memory B cell

10.1084/jem.192.12.1763

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Citations (27)

Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide

Nature Immunology (2001)

Martha S. Jordan Alina C. Boesteanu Amy J. Reed Andria L. Petrone Andrea E. Holenbeck

Negative selection

Thymocyte

Regulatory T cell

10.1038/86302

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Citations (1,660)