Flow cytometric and functional analyses of central nervous system-infiltrating cells in SJL/J mice with Theiler's virus-induced demyelinating disease. Evidence for a CD4+ T cell-mediated pathology.
Theiler's murine encephalomyelitis viruses (TMEVs) are endemic enteric pathogens of mice that cause immune-mediated, chronic, progressive, central nervous system (CNS) demyelinating disease in susceptible strains. Analysis of T cell phenotype and functional state from TMEV-infected SJL/J mice by flow cytometry reveals that 13.5 to 25% of the CD4+ T cells in the CNS express high affinity IL-2R, a marker of recent T cell activation, whereas splenic levels of CD4+IL-2R+ T cells generally range between 2 and 8.5%. In contrast, very few CD8+ T cells (<1-2%) from either site express IL-2R. From days 20 to 119 postinfection, the percentage of CD4+IL-2R+ T cells increases gradually in the CNS, but varies little in the spleen. CD4+ T cells isolated from the spinal cord of infected mice proliferate in vitro in response to viral Ag. Similar T cell phenotypes were found in experimental autoimmune encephalomyelitis, an established model of CD4+ T cell-mediated demyelination. In addition, most CD4+ and CD8+ T cells in CNS isolates from TMEV-infected mice are CD44+, indicating that prior activation may be required to traffic through and/or be retained in the CNS. Finally, TCR V beta region usage as well as IL-2R expression by individual V beta region subsets are heterogeneous in both the CNS and spleen. These results are consistent with a model in which a polyclonal population of TMEV-specific, CD4+ Th1 cells plays a major effector role in the demyelinating process.
Pope
J G
JG
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Karpus
W J
WJ
VanderLugt
C
C
Miller
S D
SD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002465:Cell Movement / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D011051:Poliomyelitis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D017945:Theilovirus / Q000276:immunology*
D018960:Hyaluronan Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2