scholarly journals Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene.

1993 ◽  
Vol 178 (2) ◽  
pp. 461-468 ◽  
Author(s):  
J Wu ◽  
T Zhou ◽  
J He ◽  
J D Mountz
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
T Cell Development ◽  
Cdna Probe ◽  
Endogenous Retrovirus ◽  
Complete Sequence ◽  
Endogenous Retroviruses ◽  
Systemic Autoimmune Disease ◽  
Polymerase Chain ◽  
Apoptosis Gene

The MRL-lpr/lpr mouse strain is a model of systemic autoimmune disease. In this model, intrinsic defects of intrathymic T cell development include defective deletion of self-reactive T cells and expression of endogenous retroviruses. Defective deletion of self-reactive T cells in the thymus has been proposed to be due to germline mutation in the Fas apoptosis gene. Using different fragments of a Fas cDNA probe, we determined that the lpr/lpr mutation is a 5.3-kb insertion of DNA within the second intron of the Fas gene. cDNA corresponding to this region was then derived from thymic RNA from MRL-lpr/lpr and MRL- +/+ mice using the polymerase chain reaction. All thymic RNA samples from MRL-lpr/lpr mice yielded a unique product that was 168 bp larger than that of MRL- +/+ mice. Complete sequence analysis indicated that this inserted sequence had 98% homology with a sequence from the 3' long terminal repeat of the early transposon (ETn). RNA analysis indicated higher expression of ETn RNA in the thymus of MRL-lpr/lpr than MRL- +/+ mice. The interdependence of ETn expression and abnormal Fas expression was then analyzed in a CD2-Fas transgenic mouse model in which a full-length murine Fas cDNA under the regulation of the CD2 promoter and enhancer was used to correct defective Fas expression in T cells of MRL-lpr/lpr mice. In these mice, reduced thymic ETn expression was observed, confirming that high ETn expression is related to abnormal Fas expression. These results establish a link between endogenous retrovirus expression, abnormal Fas expression, and autoimmune disease.

Murine systemic autoimmune disease induced by mercuric chloride (HgCl2): Hg-specific helper T-cells react to antigen stored in macrophages

1993 ◽  
Vol 15 (2) ◽  
pp. 151-161 ◽  
Author(s):  
Malgorzata Kubicka-Muranyi ◽  
Olaf Behmer ◽  
Markus Uhrberg ◽  
Hanne Klonowski ◽  
Joachim Bister ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Mercuric Chloride ◽  
Helper T Cells ◽  
Systemic Autoimmune Disease

scholarly journals Nucleosome-Specific Regulatory T Cells Engineered by Triple Gene Transfer Suppress a Systemic Autoimmune Disease

2004 ◽  
Vol 173 (3) ◽  
pp. 2118-2125 ◽  
Author(s):  
Keishi Fujio ◽  
Akiko Okamoto ◽  
Hiroyuki Tahara ◽  
Masaaki Abe ◽  
Yi Jiang ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Gene Transfer ◽  
Regulatory T Cells ◽  
Systemic Autoimmune Disease

Impaired thymic negative selection causes autoimmune graft-versus-host disease

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 429-435 ◽  
Author(s):  
Takanori Teshima ◽  
Pavan Reddy ◽  
Chen Liu ◽  
Debra Williams ◽  
Kenneth R. Cooke ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Mhc Class Ii ◽  
Graft Versus Host Disease ◽  
Negative Selection ◽  
Class Ii ◽  
Systemic Autoimmune Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Autoreactive T Cell

AbstractAnimal models with impaired thymic negative selection do not always cause autoimmune diseases despite the development of an autoreactive T-cell repertoire. We investigated the requirements for the de velopment of systemic autoimmune disease by using bone marrow chimeras that lacked expression of major histocompatibility complex (MHC) class II on thymic antigen-presenting cells (APCs), leading to impaired negative selection. We found that impaired negative selection mediated by absence of MHC class II, but not MHC class I, permitted the development of systemic autoimmune disease that is indistinguishable from acute graft-versus-host disease (GVHD). Thymectomy prevented disease, confirming the causal association of the thymus with its development. Adoptive transfer of CD4+ T cells caused GVHD in secondary hosts only when they were irradiated, and cotransfer of peripheral CD4+ and CD8+ T cells from naive mice prevented the disease. These results demonstrate that impaired thymic negative selection can cause lethal autoimmune disease indistinguishable from acute GVHD in the context of a proinflammatory milieu when peripheral regulatory mechanisms are absent.

scholarly journals Isolation and Characterization of an Infectious Replication-Competent Molecular Clone of Ecotropic Porcine Endogenous Retrovirus Class C

2006 ◽  
Vol 80 (20) ◽  
pp. 10258-10261 ◽  
Author(s):  
Thomas Preuss ◽  
Nicole Fischer ◽  
Klaus Boller ◽  
Ralf R. Tönjes
Keyword(s):  
T Cells ◽  
Genomic Library ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Miniature Swine ◽  
Infectious Risk ◽  
Isolation And Characterization ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses

ABSTRACT Xenotransplantation of pig organs is complicated by the existence of polytropic replication-competent porcine endogenous retroviruses (PERV) capable of infecting human cells. The potential for recombination between ecotropic PERV-C and human-tropic PERV-A and PERV-B adds another level of infectious risk. Proviral PERV-C were characterized in MAX-T cells derived from d/d haplotype miniature swine. Three proviruses were cloned from a genomic library. Clone PERV-C(1312) generated infectious particles after transfection into porcine ST-IOWA cells. Electron microscopy revealed the same morphologies of virions in MAX-T cells and in ST-IOWA cells infected with cell-free PERV-C(1312) particles, indicating that MAX-T cells harbor one functional PERV-C provirus.

scholarly journals Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

2022 ◽  
Vol 23 (2) ◽  
pp. 905
Author(s):  
Sunhee Jang ◽  
Eui-Jong Kwon ◽  
Jennifer Jooha Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Autoimmune Disease ◽  
Immune Cells ◽  
Cartilage Destruction ◽  
Systemic Autoimmune Disease ◽  
Pannus Formation ◽  
Systemic Complications ◽  
Tissue Proliferation ◽  
Novel Therapeutic

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.

scholarly journals Systemic Autoimmune Disease Caused by Autoreactive B Cells That Receive Chronic Help from Ig V Region-Specific T Cells

2005 ◽  
Vol 175 (4) ◽  
pp. 2391-2400 ◽  
Author(s):  
Ludvig André Munthe ◽  
Alexandre Corthay ◽  
Audun Os ◽  
Michael Zangani ◽  
Bjarne Bogen
Keyword(s):  
T Cells ◽  
B Cells ◽  
Autoimmune Disease ◽  
Systemic Autoimmune Disease ◽  
Autoreactive B Cells ◽  
V Region

scholarly journals Functional Analysis of the env Open Reading Frame in Human Endogenous Retrovirus IDDMK1,222 Encoding Superantigen Activity

2000 ◽  
Vol 74 (14) ◽  
pp. 6386-6393 ◽  
Author(s):  
Matthias Lapatschek ◽  
Susanne Dürr ◽  
Roswitha Löwer ◽  
Christine Magin ◽  
Hermann Wagner ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Expression Vectors ◽  
Human Endogenous Retrovirus ◽  
Human Major Histocompatibility Complex ◽  
Reading Frame

ABSTRACT Mice harbor a family of endogenous retroviruses, the mouse mammary tumor viruses (MMTV), which encode superantigens. These superantigens are responsible for the deletion of T cells expressing certain Vβ chains of the T-cell receptor in the thymus. Human T cells are able to recognize MMTV-encoded superantigens presented by human major histocompatibility complex class II-positive cells. Owing to this and to the similarity of the human and murine immune systems, it was speculated that human endogenous retroviruses might also code for superantigens. Recently, it was reported that a proviral clone (IDDMK1,222) of the human endogenous retrovirus family HTDV/HERV-K encodes a superantigen. The putative superantigen gene was located within the env region of the virus. Stimulated by these findings, we amplified by PCR and cloned into eucaryotic expression vectors open reading frames (ORFs) which were identical or very similar to IDDMK1,222. When we transfected these vectors into A20 cells, a murine B-cell lymphoma, we were able to demonstrate mRNA expression and protein production. However, we did not find any evidence that the ORF stimulated human or murine T cells in a Vβ-specific fashion, the most prominent feature of superantigens.

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