Murine gammaherpesvirus-induced splenomegaly: a critical role for CD4 T cells

Murine gammaherpesvirus (MHV-68) causes an acute respiratory infection followed by a latent infection in B lymphocytes. In the first 23 weeks after infection mice develop a marked splenomegaly, where the spleen cell number increases by 23-fold. Cytofluorimetric analysis during splenomegaly revealed an increase in numbers of B lymphocytes and of both CD4⁺ and CD8⁺ T lymphocytes. The largest increase relative to uninfected spleens was in the CD8⁺ population. The number of latently infected cells in the spleen peaked at day 10 post-intraperitoneal infection, then declined to 1/10⁶1/10⁷ cells per spleen. Depletion of CD4⁺ T lymphocytes prevented the splenomegaly and greatly reduced the peak infective centre level, while having no effect on the long-term level of latently infected cells. Given the similarity between MHV-68-induced splenomegaly and Epstein-Barr virus-induced infectious mononucleosis, these data highlight the usefulness of MHV-68 as a mouse model for the study of gammaherpesvirus immunology and pathobiology.

^* Author for correspondence. Fax +44 131 650 6511. e-mail EJU@lab0.vet.ed.ac.uk