MHC class I gene(s) in the D/L region but not the TNF-α gene determines development of toxoplasmic encephalitis in mice

Yasuhiro Suzuki, Kensuke Joh, Oh Chol Kwon, Qing Yang, Frances K. Conley, Jack S. Remington

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Previous studies revealed that mice with the b or k allele at the H-2D region are susceptible to toxoplasmic encephalitis (TE); those with the d allele are resistant. To determine whether the b or d allele is dominant, F1 hybrids between susceptible C57BL/6 (H-2(b)) and resistant BALB/c (H-2(d)) mice were infected with T. gondii. TE was not observed in the F1 hybrids, indicating that the d allele is dominant for protection against development of TE. Mice with a mutation in the D/L region were used to determine whether the D gene or the L gene of MHC class I Ags of the H-2D region is most critical for resistance against development of TE. B10.D2-H-2(dm1) (dm1) mice that have the mutant D/L hybrid gene formed by fusion of the 5' part of the D(d) gene and the 3' part of the L(d) gene developed TE in contrast to their background B10.D2 mice. BALB/c-H-2(dm2) (dm2) mice, which have a complete deletion of the L(d) gene, had significantly more T. gondii cysts in their brains than did dm1 mice and developed large areas of necrosis in their brains that were not observed in dm1 mice. These results indicate that a gene(s) in the D/L region determines whether TE will occur and that the L(d) gene plays a critical role in the resistance against development of TE. Polymorphisms in the TNF-α gene (located in the H-2D region) have been reported to correlate with resistance against the development of TE. When development of TE was studied in BALB/c and dm2 mice that have the same TNF- α gene, only dm2 mice developed TE. This indicates that the TNF-α gene is not a determining factor for the development of TE. Transcripts for TNF-α were detected in brains of infected dm2 mice but not in BALB/c mice. Injection of neutralizing Abs against TNF-α resulted in worsening of the TE in infected dm2 mice but did not induce TE in infected BALB/c mice. Thus, TNF-α appears to be produced in the brain after TE has developed and is responsible for preventing the progression of TE.

Original languageEnglish
Pages (from-to)4649-4654
Number of pages6
JournalJournal of Immunology
Volume153
Issue number10
StatePublished - Nov 15 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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