Resistance to Marek's disease herpesvirus-induced lymphoma is multiphasic and dependent on host genotype

Genotype-dependent differences in Marek's disease (MD) susceptibility were identified using 14-day-old line N and 6(1) (resistant) and 15I and 7(2) (s usceptible) inbred chickens infected with HPRS-16 MD virus (MDV). All line 7(2) chickens developed progressive MD. Line 15I had fluctuating MD-specifi c clinical signs and individuals recovered. A novel histologic scoring syst em enabled indices to be calculated for lymphocyte infiltration into nonlym phoid organs. All genotypes had increased mean lesion scores (MLSs) and mea n total lesion scores after MDV infection. These differed quantitatively an d qualitatively between the genotypes. Lines 6(1) and 7(2) had a similar ML S distribution in the cytolytic phase, although scores were greater in line 7(2). At the time lymphomas were visible in line 7(2), histologic lesions in line 6(1) were regressing. AV37(+) cells were present in similar numbers in all genotypes in the cytolytic phase, suggesting that neoplastically tr ansformed cells were present in all genotypes regardless of MD susceptibili ty. After the cytolytic phase, AV37(+) cell numbers increased in lines 7(2) and 15I but decreased in lines 6(1) and N. In the cytolytic and latent pha ses, in all genotypes, most infiltrating cells were CD4(+). After this time , line 7(2) and 15I lesions increased in size and most cells were CD4(+); l ine 6(1) and N lesions decreased in size and most cells were CD8(+). In all genotypes, AV37 immunostaining was weak in lesions with many CD8(+) cells, suggesting that AV37 antigen expression or AV37(+) cells were controlled b y CD8(+) cells. The rank order, determined by clinical signs and pathology, for MD susceptibility (highest to lowest) was 7(2) > 15I > 6(1) > N.