Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody

Perlman, Stanley; Schelper, Robert L.; Bolger, E.; Ries, Dana

doi:10.1016/0882-4010(87)90020-9

Cited by 101 publications

(139 citation statements)

References 22 publications

Supporting

Mentioning

136

Contrasting

Order By: Relevance

“…Virus was grown and titered as previously described (17). Wild-type MHV-JHM was used to immunize wild-type B6 donor mice, as previously described (1).…”

Section: Virusmentioning

confidence: 99%

CD4 and CD8 T Cells Have Redundant But Not Identical Roles in Virus-Induced Demyelination

Wu¹,

Dandekar

Pewe

et al. 2000

The Journal of Immunology

187

282

View full text Add to dashboard Cite

A chronic demyelinating disease results from murine infection with the neurotropic strain JHM of mouse hepatitis virus (MHV-JHM). Demyelination is largely immune mediated. In this study, the individual roles of CD4 and CD8 T cells in MHV-induced demyelination were investigated using recombination-activating gene 1−/− (RAG1−/−) mice infected with an attenuated strain of MHV-JHM. These animals develop demyelination only after adoptive transfer of splenocytes from mice previously immunized to MHV. In this study, we show that, following adoptive transfer, virus-specific CD4 and CD8 T cells rapidly infiltrate the CNS of MHV-JHM-infected RAG1−/− mice. Adoptive transfer of CD4 T cell-enriched donors resulted in more severe clinical disease accompanied by less demyelination than was detected in the recipients of undepleted cells. Macrophage infiltration into the gray matter of CD4 T cell-enriched recipients was greater than that observed in mice receiving undepleted splenocytes. In contrast, CD8 T cell-enriched recipients developed delayed disease with extensive demyelination of the spinal cord. MHV-JHM-infected RAG1−/− mice receiving donors depleted of both CD4 and CD8 T cells did not develop demyelination. These results demonstrate that the development of demyelination following MHV infection may be initiated by either CD4 or CD8 T cells. Furthermore, they show that CD4 T cells contribute more prominently than CD8 T cells to the severity of clinical disease, and that this correlates with increased macrophage infiltration into the gray matter.

show abstract

“…Virus was grown and titered as previously described (17). Wild-type MHV-JHM was used to immunize wild-type B6 donor mice, as previously described (1).…”

Section: Virusmentioning

confidence: 99%

CD4 and CD8 T Cells Have Redundant But Not Identical Roles in Virus-Induced Demyelination

Wu¹,

Dandekar

Pewe

et al. 2000

The Journal of Immunology

187

282

View full text Add to dashboard Cite

show abstract

“…Nonrecombinant and recombinant JHM were grown and titered as previously described (8). Virus was harvested from infected brains and spinal cords as previously described (8).…”

Section: Virus and Cellsmentioning

confidence: 99%

“…Mice infected with JHM develop an acute, fatal encephalitis or acute or chronic demyelinating diseases, dependent upon the conditions of the infection (7). In one model, suckling C57BL/6 (B6) mice were infected with JHM and nursed by dams previously immunized to the virus (8). Nursing by immunized dams prevented acute encephalitis, but 40 -90% of the suckling mice developed a demyelinating encephalomyelitis with clinical signs of hindlimb paralysis several weeks p.i.…”

mentioning

confidence: 99%

Protection Against CTL Escape and Clinical Disease in a Murine Model of Virus Persistence

Kim¹,

Perlman

2003

The Journal of Immunology

View full text Add to dashboard Cite

CTL escape mutations have been identified in several chronic infections, including mice infected with mouse hepatitis virus strain JHM. One outstanding question in understanding CTL escape is whether a CD8 T cell response to two or more immunodominant CTL epitopes would prevent CTL escape. Although CTL escape at multiple epitopes seems intuitively unlikely, CTL escape at multiple CD8 T cell epitopes has been documented in some chronically infected individual animals. To resolve this apparent contradiction, we engineered a recombinant variant of JHM that expressed the well-characterized gp33 epitope of lymphocytic choriomeningitis virus, an epitope with high functional avidity. The results show that the presence of a host response to this second epitope protected mice against CTL escape at the immunodominant JHM-specific CD8 T cell epitope, the persistence of infectious virus, and the development of clinical disease.

show abstract

“…Mice or rats infected in the presence of maternal immunity specific for MHV-JHM developed demyelinating disease several weeks later (Wege et al, 1981 ;Perlman et al, 1987). Experiments in which lymphocyte subpopulations were transferred into rats immunosuppressed by irradiation have been done recently (Schwender et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, there is evidence that the immune response is able to promote the establishment of a chronic demyelinating disease associated with virus persistence (Shubin et al, 1990;Wang et al, 1990). Suckling mice and rats nursed by immune mothers can develop a subacute disease after infection with an otherwise lethal dose of MHV-JHM, indicating that IgG in the milk may contribute to the course of disease (Perlman et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Coronavirus-induced encephalomyelitis: balance between protection and immune pathology depends on the immunization schedule with spike protein S

Flory¹,

Stühler²,

Barac-Latas³

et al. 1995

Journal of General Virology

View full text Add to dashboard Cite

The neurotropic mouse hepatitis virus MHV-JHM induces central nervous system (CNS) demyelination in Lewis rats that pathologically resembles CNS lesions in multiple sclerosis. The mechanisms of MHV-JHMinduced demyelination remain unclear and several studies have implicated the role of the immune response in this process. We have shown previously that protective immunity against MHV-JHM-induced encephalomyelitis was induced by immunization with a vaccinia virus (VV) recombinant expressing MHV-JHM Sprotein (VV-S). Here, we present evidence that the time of MHV-JHM challenge after immunization with VV-S plays a critical role in protective immunity. The induction of virus-neutralizing S-protein-specific antibodies prior to the MHV-JHM challenge modulates the disease process and a subacute encephalomyelitis based on a persistent virus infection developed. Typical pathological alterations were lesions of inflammatory demyelination. In addition, the results indicate that after seroconversion, CD8 ÷ T cells were no longer essential for virus elimination in contrast to their role in protection during acute encephalomyelitis.

show abstract

Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody

Cited by 101 publications

References 22 publications

CD4 and CD8 T Cells Have Redundant But Not Identical Roles in Virus-Induced Demyelination

CD4 and CD8 T Cells Have Redundant But Not Identical Roles in Virus-Induced Demyelination

Protection Against CTL Escape and Clinical Disease in a Murine Model of Virus Persistence

Coronavirus-induced encephalomyelitis: balance between protection and immune pathology depends on the immunization schedule with spike protein S

Contact Info

Product

Resources

About