Exacerbation of murine herpes simplex virus-mediated stromal keratitis by Th2 type T cells.
Corneal infection of susceptible mice with HSV-1 causes herpetic stromal keratitis (HSK), which serves as a model of human HSK. To study the properties of the T lymphocytes involved in HSK, susceptible mice were immunized with the synthetic peptide corresponding to the amino terminal of HSV-1-associated glycoprotein D (gD 5-23). A CD4+ long-term T cell line and a clone bearing V beta 8.2 TCR were derived from peptide-primed lymph node cells. These T cells recognize gD 5-23 peptide in the context of I-Ed and require CD4 and LFA-1 for Ag-specific proliferation. Significantly, a truncated peptide gD 15-23 induced vigorous proliferation, indicating that these 9 amino acids constitute an epitope recognized by these T cells. The gD-specific T cells produced IL-4 and used it as the autocrine growth factor and hence belong to the Th2 subtype. Adoptive transfer of gD-specific Th2 cells into susceptible mice increased both the onset and severity of HSK after corneal HSV-1 infection. Injection of gD-specific Th2 cells without HSV-1 infection failed to cause eye damage. In addition, an irrelevant Ag-specific Th2 clone failed to induce similar tissue damage when the corresponding Ag was applied to the eye. These data indicate that the T cell-mediated exacerbation of HSK in these studies is dependent on the specific recognition of gD after corneal HSV-1 infection. Finally, gD-specific Th2 cell transfer also rendered HSK-resistant mice susceptible for HSK, suggesting that the freedom from HSK in resistant mice may primarily be due to their inability to produce the pathogenic Th2 cells. The data collectively implicate an important role for Th2 cells in the induction of HSV-mediated keratitis in mice.
Jayaraman
S
S
Division of Clinical Virology, James N. Gamble Institute of Medical Research, Cincinnati, OH 45219.
Heiligenhaus
A
A
Rodriguez
A
A
Soukiasian
S
S
Dorf
M E
ME
Foster
C S
CS
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D016849:Keratitis, Herpetic / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D015847:Interleukin-4