Persistence of Lymphocytic Choriomeningitis Virus in Immune Animals and Its Relation to Immunity

Traub, E.

doi:10.1084/jem.63.6.847

Cited by 141 publications

(60 citation statements)

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“…Chronic infection of mice with LCMV has long been a classic model of immunological tolerance (1)(2)(3). Congenitally infected mice are first exposed to the virus during embryonic life and viral antigen is present in the fetal thymus.…”

Section: Discussionmentioning

confidence: 99%

T-cell tolerance: exposure to virus in utero does not cause a permanent deletion of specific T cells.

Jamieson

Ahmed

1988

Proc. Natl. Acad. Sci. U.S.A.

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This study documents the curing of a congenitally acquired chronic viral infection and the acquisition of T-cell competence by a previously tolerant host. Infection of mice with lymphocytic choriomeningitis virus (LCMV) is a classic model of viral persistence and antigen-specific T-celi unresponsiveness. Mice infected at birth or in utero become lifelong carriers with no detectable virus-specific cytotoxic T lymphocyte (CTL) responses. This chronic infection can be eliminated by adoptive transfer of Lyt-2+ T cells from LCMVimmune mice. To determine whether these cured carriers were capable of generating their own LCMV-specific CTL response, mice congenic at the Thy-i locus (Thy-1.1 and Thy-1.2) were used in the adoptive transfer experiments. Hostderived T-cell responses were checked after treating the cured carriers with a monoclonal antibody to deplete the immune donor T cells. Such cured carrier mice were able to generate a host-derived virus-specific CTL response and resisted a second LCMV challenge in the absence of any donor T cells. In addition, bone marrow cells from these cured carriers could functionally reconstitute irradiated mice. Thus this report demonstrates the acquisition of LCMV-specific T-cell competence by previously unresponsive carrier mice infected in utero. These results show that exposure to a virus even during embryonic life does not cause a permanent deletion of specific T cells. These findings are of significance to the understanding of tolerance mechanisms and have implications for the treatment of chronic viral infections.Congenitally acquired chronic infection of mice with lymphocytic choriomeningitis virus (LCMV) is a classic model of immunological tolerance and viral persistence. The prediction of Burnet and Fenner (1) that an antigen introduced into the body during embryonic life would be mistaken for self, and Burnet's (2) theory of clonal deletion of self-reactive clones, were partly based on Traub's (3) studies on congenital infection of mice with LCMV. The other finding that led Burnet and Fenner to postulate the concept of immunological tolerance to antigens encountered during ontogeny was Owen's (4) observations that dizygotic cattle twins sharing vascular supplies in utero developed into erythrocyte chimeras.Mice infected with LCMV at birth or in utero become lifelong carriers, with high levels of infectious virus in most of their organs. Although such persistently infected mice make virus-specific antibody responses (5), attempts by several investigators to demonstrate virus-specific T cells have been mostly unsuccessful (6-11). These carrier mice show minimal or no detectable cytotoxic-T-lymphocyte (CTL) or delayedtype-hypersensitivity (DTH) responses against LCMV, and they also show either a paucity or a lack of T cells that will proliferate when stimulated with the virus. In this study, we demonstrate the acquisition of T-cell competence in mice cured of congenitally acquired chronic LCMV infection. The cured carrier mice can generate a host-derived-virus-spec...

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Section: Discussionmentioning

confidence: 99%

T-cell tolerance: exposure to virus in utero does not cause a permanent deletion of specific T cells.

Jamieson

Ahmed

1988

Proc. Natl. Acad. Sci. U.S.A.

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“…One example was the continuing coexistence of genetically disparate blood cells in cattle twins that had had a common placental cir culation [Owen. 1945], and the other was the persistent infection of LCM virus in mice that had made contact with the agent before or immediately after birth [Traub. 1936[Traub.…”

Section: Cellular Immune Responses To Arenavi Rusesmentioning

confidence: 99%

“…Two forms of persistent infection of Mus musculus with LCM virus [Traub, 1936[Traub, , 1939 should be clearly distinguished. One form is the 'persistent tolerant infection' of carrier mice [Hotchin.…”

Section: Persistent Infectionmentioning

confidence: 99%

“…However, not all LCM virus-carrier mice are free from disease. Kidney lesions were recognized by Traub [1936], and these, together with their functional consequences, have remained the predominant signs in LCM virus-carrier mice suffering from the so-called late-onset disease [Hotchin and Collins. 1964], although numerous other tissues are also involved.…”

Section: Persistent Infectionmentioning

confidence: 99%

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Portraits of Viruses: Arenaviruses

Lehmann-Grube¹

1984

Intervirology

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“…First, chronic LCM infection per se usually is not associated with cytopathogenicity. Mice persistently infected with LCM (LCM carriers) of most strains demonstrate high titers of virus in virtally all tissues and yet most of these tissues show little, if any, evidence of cellular injury (1)(2)(3)(4)(5)(6). Also, LCM infection of a variety of cells in tissue culture is usually not accompanied by cell injury despite active viral replication (7)(8)(9)(10).…”

mentioning

confidence: 99%

Pathogenesis of Chronic Disease Associated With Persistent Lymphocytic Choriomeningitis Viral Infection

Oldstone

Dixon

1970

The Journal of Experimental Medicine

123

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Tissue injury (chronic disease) associated with persistent LCM infection is apparently caused by the host immune response to the virus. Employing parabiosis or cell transfer from hyperimmune donors to isologous virus carriers, the tissue injury of chronic disease could be initiated and/or intensified. Furthermore, the transfer of anti-LCM antibody to SWR/J carrier mice results in acute necrotizing inflammatory lesions in regions of viral persistence, followed by chronic mononuclear infiltrates quite similar to those seen after the transfer of immune cells. The pathogenesis of the nonglomerular tissue injury of chronic LCM disease is apparently at least in part related to the interaction of circulating anti-LCM antibody with viral antigen at the tissue site. Trapping of circulating virus-antibody complexes in the glomerular filter is apparently the major cause of the glomerulonephritis.

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Persistence of Lymphocytic Choriomeningitis Virus in Immune Animals and Its Relation to Immunity

Cited by 141 publications

References 0 publications

T-cell tolerance: exposure to virus in utero does not cause a permanent deletion of specific T cells.

T-cell tolerance: exposure to virus in utero does not cause a permanent deletion of specific T cells.

Portraits of Viruses: Arenaviruses

Pathogenesis of Chronic Disease Associated With Persistent Lymphocytic Choriomeningitis Viral Infection

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