Preferential induction of IL-10 in APC correlates with a switch from TH1 to TH2 response following infection with a low pathogenic variant of Theiler's virus

Jo Ann P. Palma, Robert L. Yauch, Hee Kap Kang, Hee Gu Lee, Byung S. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Theiler's murine encephalomyelitis virus induces immune-mediated demyelination in susceptible mice after intracerebral inoculation. A naturally occurring, low pathogenic Theiler's murine encephalomyelitis virus variant showed a single amino acid change within a predominant Th epitope from lysine to arginine at position 244 of VP1. This substitution is the only one present in the entire viral capsid proteins. In this paper, we demonstrate that the majority of T cells specific for VP1233-250 and VP274-86 from wild-type virus-infected mice are Th1 type and these VP1-specific cells poorly recognize the variant VP1 epitope (VP1K244R) containing the substituted arginine. In contrast, the Th2-type T cell population specific for these epitopes predominates in variant virus-infected mice. Immunization with UV-inactivated virus or VP1 epitope peptides could not duplicate the preferential Th1/Th2 responses following viral infection. Interestingly, the major APC populations, such as dendritic cells and macrophages, produce IL-12 on exposure to the pathogenic wild-type virus, whereas they preferentially produce IL-10 in response to the low pathogenic variant virus. Thus, such a spontaneous mutant virus may have a profoundly different capability to induce Th-type responses via selective production of cytokines involved in T cell differentiation and the consequent pathogenicity of virally induced immune-mediated inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)4221-4230
Number of pages10
JournalJournal of Immunology
Volume168
Issue number8
DOIs
StatePublished - Apr 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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