Bystander activation of CD4(+) T cells can represent an exclusive means of immunopathology in a virus infection

Eur J Immunol. 1999 Nov;29(11):3674-82. doi: 10.1002/(SICI)1521-4141(199911)29:11<3674::AID-IMMU3674>3.0.CO;2-7.


Herpetic stromal keratitis (HSK) is an immunopathological lesion involving herpes simplex virus (HSV) infection and CD4(+) T cells of the Th1 phenotype, but the nature of the target antigens which drive HSK remains uncertain. In the present report we show that ovalbumin TCR-transgenic mice backcrossed to SCID mice unable to recognize HSV show clinical signs of HSK but die of viral encephalitis before the lesions become severe. However, passive transfer of anti-HSV serum at 24 h clears virus and affords protection from both HSK lesions and death. Adoptive transfer of CD8(+) T cells at 72 h usually conferred protection but animals developed severe corneal pathology by 3 weeks post infection. At this time viral antigens were not demonstrable in the cornea and the T cells in the inflammatory lesions were CD4(+)KJ1-26.1 idiotype positive, i. e. OVA peptide specific. These results indicate bystander activation of CD4(+) T cells in a virus-induced inflammatory milieu. This mechanism of immunoinflammation may represent an important component of any lesion which involves CD4(+) T cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Encephalitis, Viral / immunology
  • Female
  • Herpesvirus 1, Human / immunology*
  • Immunization, Passive
  • Keratitis, Herpetic / immunology*
  • Keratitis, Herpetic / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mice, Transgenic


  • Antibodies, Viral