IgG subclass responses to Theiler's murine encephalomyelitis virus infection and immunization suggest a dominant role for Th1 cells in susceptible mouse strains.
Inbred mouse strains differ in susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. A strong correlation between disease susceptibility and delayed-type hypersensitivity (DTH) has been previously demonstrated, but no strong correlation between disease susceptibility and total anti-TMEV ELISA titres was shown. Since both DTH and IgG2a antibody production are regulated by CD4+ Th1 cells, we investigated three strains of mice to determine whether antivirus IgG2a antibody levels, like DTH in previous studies, correlated with disease susceptibility. Susceptible SJL/J, intermediately susceptible C3H/HeJ, and resistant C57BL/6 mice were infected intracerebrally (i.c.) with the BeAn strain of TMEV and monitored for clinical signs of demyelination and for levels of TMEV-specific antibody of different IgG subclasses using a particle concentration fluorescence immunoassay (PCFIA). Resistant C57BL/6 mice were found to have significantly lower concentrations of total anti-TMEV antibody than susceptible SJL/J mice and intermediately susceptible C3H/HeJ mice show variable antibody responses. A predominance of anti-TMEV IgG2a (Th1 regulated) antibody was seen in susceptible and intermediately susceptible mice, whereas resistant mice displayed a predominant anti-TMEV IgG1 (Th2 regulated) response accompanied by a marked deficiency of IgG2a. In contrast, immunization of C57BL/6 mice with UV-inactivated TMEV in adjuvant revealed that this strain was not defective either in its ability to generate high levels of anti-TMEV antibody or in its ability to produce IgG2a antibody. These results suggest that the antivirus IgG subclass profile is dependent upon the immunization route, virus viability and/or the use of adjuvant and that the levels of antivirus subclasses may be predictive of disease susceptibility.
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611.
J D
JD
Peterson
C
C
Waltenbaugh
S D
SD
Miller
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000918:Antibody Specificity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004198:Disease Susceptibility; D004769:Enterovirus Infections / Q000276:immunology*; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis*; D004680:Maus Elberfeld virus / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains
D000914:Antibodies, Viral; D007074:Immunoglobulin G