Activation of C-type viruses during skin graft rejection in the mouse. Interrelationships between immunostimulation and immunosuppression.

Both mouse-tropic and zenotropic C-type RNA viruses were activated in BALB/c mice during rejection reactions against skin grafts from mice differing at the major histocompatibility locus (A/J) or sharing this locus (DBA/2). Animals that maintained their skin grafts following immunosuppression with antilymphocyte serum (ALS) or cyclophosphamide had a much higher incidence of virus-positivity than animals that did not receive ALS or cyclophosphamide, or that rejected their skin grafts despite immunosuppressive therapy. ALS itself activated type-C viruses from a small proportion of BALB/c mice whereas cyclophoshamide alone did not. Type C viruses were detected in spleens and regional nodes draining skin-graft sites between 1 and 2 weeks following transplantation; thereafter they reached maximum titers in spleens. Viruses were not detected at skin-graft sites, in tails or in thymuses of grafted animals. Virus activation was associated with splenic histological changes consisting of germinal center formation, diffuse hyperplasia of reticulum cells, depletion of periarteriolar lymphocytes and hyperplasia of red pulp hematopoietic elements.