Lymphocyte-mediated immune cytotoxicity in dogs infected with virulent canine distemper virus

Immune lymphocyte-mediated cytotoxicity (ILMC) was evaluated in dogs after intranasal exposure to one of the following three virulent strains of canine distemper virus: Cornell A75/17, Ohio R252, and Snyder Hill. Cytotoxicity was tested with peripheral blood lymphocytes as effector cells and primary dog testicle cells that were matched for histocompatibility as target cells. A strong correlation was found between ILMC and the course of the infection. Dogs that succumbed to encephalitis with any of the strains had little or no ILMC, whereas dogs that recovered had the highest activity. In the intermediate range were dogs with a delayed or reduced ILMC which developed persistent but subclinical central nervous system infections. A significant difference in onset, peak, and duration of ILMC was observed in dogs infected with different strains of canine distemper virus. ILMC responses began at 14 days postinfection (p.i.), reached a peak at 21 to 28 days p.i., and returned to preinoculation levels by 63 to 70 days p.i. in canine distemper virus A75/17- and R252-infected dogs. In contrast, ILMC in canine distemper virus Snyder Hill-infected dogs began at 10 days p.i., peaked by 14 to 17 days p.i., and approached preinoculation levels by 28 days p.i. Antiviral immunity as measured by ILMC appears to be a critical factor in determining the outcome in canine distemper virus-infected hosts. Furthermore, for certain viral biotypes, a delayed ILMC response correlated with persistent infection of the central nervous system.