TY - JOUR
T1 - Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. II. Survey of host immune responses and central nervous system virus titers in inbred mouse strains
AU - Clatch, Richard J.
AU - Lipton, Howard L.
AU - Miller, Stephen D.
N1 - Funding Information:
"This work was supported in part by U .S . Public Health Service Grants NS-23349, NS-21913, National Multiple Sclerosis Society Grant RG-1487, and Northwestern University BRSG Award 8529 . tAbbreviations used in this paper : CFA, complete Freund's adjuvant ; CMI, cell-mediated immunity ; CNS, central nervous system; CPM, counts per minute; CTL, cytotoxic T lymphocytes; DMEM, Dulbecco's modified Eagle medium; DTH, delayed-type hypersensitivity; ELISA, enzyme-linked immunosorbent assay; i .c ., intracerebral ; LN, lymph node ; MHC, major histocompatibility complex ; p.i ., post-infection ; s .c . subcutaneous ; SI, stimulation index ; Tprlf, proliferating T cells ; TMEV, Theiler's murine encephalomyelitis virus ; Ts, suppressor T cells .
PY - 1987/11
Y1 - 1987/11
N2 - Previous studies using mouse strains with limited genetic differences and H-2 haplotypes demonstrated that susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demylinating disease strongly correlated with chronically high levels of TMEV-specific delayed-type hypersensitivity (DTH), but not with TMEV-specific T cell proliferation (Tprlf), serum antibody responses, or with CNS virus titers. To determine if this correlation would be supported by analysis of these parameters in a more thorough genetic survey, ten inbred mouse strains, representing a wide variety of genetic backgrounds and H-2 haplotypes, were inoculated intracerebrally (i.c.) with the BeAn strain of TMEV. Significant TMEV-specific DTH was observed in all highly susceptible strains, but was not detectable in intermediate and resistant strains. TMEV-specific serum antibody titers also appeared to correlate with susceptibility to demyelinating disease, however even resistant strains had high antibody responses. Significant differences in CNS TMEV titers existed between strains, but did not correlate with disease susceptibility. DTH and Tprlf responses were observed in 3 4 resistant strains following peripheral immunization with UV-inactivated TMEV indicating that most resistant strains are genetically capable of mounting virus-specific cell-mediated immune (CMI) responses. The data extends our knowledge of host immune responses and virus titers in many different inbred mouse strains persistentlty infected with TMEV, supports the hypothesis that the demyelination in highly susceptible mice involves a TMEV-specific DTH response, and suggests that the genetic ability to mount specific DTH responses is necessary, but not sufficient for development of the demyelinating disease.
AB - Previous studies using mouse strains with limited genetic differences and H-2 haplotypes demonstrated that susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demylinating disease strongly correlated with chronically high levels of TMEV-specific delayed-type hypersensitivity (DTH), but not with TMEV-specific T cell proliferation (Tprlf), serum antibody responses, or with CNS virus titers. To determine if this correlation would be supported by analysis of these parameters in a more thorough genetic survey, ten inbred mouse strains, representing a wide variety of genetic backgrounds and H-2 haplotypes, were inoculated intracerebrally (i.c.) with the BeAn strain of TMEV. Significant TMEV-specific DTH was observed in all highly susceptible strains, but was not detectable in intermediate and resistant strains. TMEV-specific serum antibody titers also appeared to correlate with susceptibility to demyelinating disease, however even resistant strains had high antibody responses. Significant differences in CNS TMEV titers existed between strains, but did not correlate with disease susceptibility. DTH and Tprlf responses were observed in 3 4 resistant strains following peripheral immunization with UV-inactivated TMEV indicating that most resistant strains are genetically capable of mounting virus-specific cell-mediated immune (CMI) responses. The data extends our knowledge of host immune responses and virus titers in many different inbred mouse strains persistentlty infected with TMEV, supports the hypothesis that the demyelination in highly susceptible mice involves a TMEV-specific DTH response, and suggests that the genetic ability to mount specific DTH responses is necessary, but not sufficient for development of the demyelinating disease.
KW - Delayed-type hypersensitivity
KW - Theiler's virus
KW - demyelination
KW - picornavirus
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U2 - 10.1016/0882-4010(87)90003-9
DO - 10.1016/0882-4010(87)90003-9
M3 - Article
C2 - 2849024
AN - SCOPUS:0023452839
SN - 0882-4010
VL - 3
SP - 327
EP - 337
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
IS - 5
ER -