Transgenic mice expressing the E7 protein of HPV16 from the keratin 14 promoter 
demonstrate increasing thymic hypertrophy with age. This hypertrophy is 
associated with increased absolute numbers of all thymocyte types, and with 
increased cortical and medullary cellularity. In the thymic medulla, increased 
compartmentalization of the major thymic stromal cell types and expansion of 
thymic epithelial cell population is observed. Neither an increased rate of 
immature thymocyte division nor a decreased rate of immature thymocyte death was 
able to account for the observed hypertrophy. Thymocytes with reduced levels of 
expression of CD4 and/or CD8 were more abundant in transgenic (tg) mice and 
became increasingly more so with age. These thymic SP and DP populations with 
reduced levels of CD4 and/or CD8 markers had a lower rate of apoptosis in the tg 
than in the non-tg mice. The rate of export of mature thymocytes to peripheral 
lymphoid organs was less in tg animals relative to the pool of available mature 
cells, particularly for the increasingly abundant CD4lo population. We therefore 
suggest that mature thymocytes that would normally die in the thymus gradually 
accumulated in E7 transgenic animals, perhaps as a consequence of exposure to a 
hypertrophied E7-expressing thymic epithelium or to factors secreted by this 
expanded thymic stromal cell population. The K14E7 transgenic mouse thus 
provides a unique model to study effects of the thymic epithelial cell 
compartment on thymus development and involution.