Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination.
J Immunol. 2000 Aug 15;165(4):2278-86. Unique Identifier : AIDSLINE MED/20384827 Wu GF; Dandekar AA; Pewe L; Perlman S; Program in Neuroscience, Departments of Pediatrics and; Microbiology, and University of Iowa College of Medicine,; University of Iowa, Iowa City, IA 52242, USA.
Abstract:
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.
Keywords: JOURNAL ARTICLE Adoptive Transfer/METHODS Animal Cell Movement/IMMUNOLOGY Comparative Study Coronavirus Infections/*IMMUNOLOGY/PATHOLOGY/*VIROLOGY CD4-Positive T-Lymphocytes/*IMMUNOLOGY/PATHOLOGY/TRANSPLANTATION CD8-Positive T-Lymphocytes/*IMMUNOLOGY/PATHOLOGY/TRANSPLANTATION Demyelinating Diseases/*IMMUNOLOGY/PATHOLOGY/*VIROLOGY Disease Models, Animal Epitopes, T-Lymphocyte/IMMUNOLOGY Gastroenteritis Virus, Murine/*IMMUNOLOGY Mice Mice, Inbred C57BL Mice, Knockout Spinal Cord/IMMUNOLOGY/PATHOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocyte Subsets/IMMUNOLOGY/PATHOLOGY/TRANSPLANTATION Viral Load
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Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
