CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination.
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.
Program in Neuroscience, Departments of Pediatrics and Microbiology, and University of Iowa College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
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Wu
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Dandekar
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Pewe
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Perlman
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002465:Cell Movement / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D019562:Viral Load
D018984:Epitopes, T-Lymphocyte