PMID- 10925317 OWN - NLM STAT- MEDLINE DCOM- 20000914 LR - 20190515 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 165 IP - 4 DP - 2000 Aug 15 TI - CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination. PG - 2278-86 AB - 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. FAU - Wu, G F AU - Wu GF AD - Program in Neuroscience, Departments of Pediatrics and Microbiology, and University of Iowa College of Medicine, University of Iowa, Iowa City, IA 52242, USA. FAU - Dandekar, A A AU - Dandekar AA FAU - Pewe, L AU - Pewe L FAU - Perlman, S AU - Perlman S LA - eng GR - MH2066-03/MH/NIMH NIH HHS/United States GR - NS36592/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Epitopes, T-Lymphocyte) SB - IM MH - Adoptive Transfer/methods MH - Animals MH - CD4-Positive T-Lymphocytes/*immunology/pathology/transplantation MH - CD8-Positive T-Lymphocytes/*immunology/pathology/transplantation MH - Cell Movement/immunology MH - Coronavirus Infections/*immunology/pathology/*virology MH - Demyelinating Diseases/*immunology/pathology/*virology MH - Disease Models, Animal MH - Epitopes, T-Lymphocyte/immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Murine hepatitis virus/*immunology MH - Spinal Cord/immunology/pathology MH - T-Lymphocyte Subsets/immunology/pathology/transplantation MH - Viral Load EDAT- 2000/08/05 11:00 MHDA- 2000/09/19 11:01 CRDT- 2000/08/05 11:00 PHST- 2000/08/05 11:00 [pubmed] PHST- 2000/09/19 11:01 [medline] PHST- 2000/08/05 11:00 [entrez] AID - ji_v165n4p2278 [pii] AID - 10.4049/jimmunol.165.4.2278 [doi] PST - ppublish SO - J Immunol. 2000 Aug 15;165(4):2278-86. doi: 10.4049/jimmunol.165.4.2278.