PATHOLOGICAL-CHANGES IN THE SPLEENS OF GAMMA-INTERFERON RECEPTOR-DEFICIENT MICE INFECTED WITH MURINE GAMMAHERPESVIRUS - A ROLE FOR CD8 T-CELLS

Murine gammaherpesvirus is a natural rodent pathogen which causes a pr imary infection in the lungs and establishes a persistent infection in B lymphocytes. During the primary infection, large amounts of gamma i nterferon (IFN-gamma) are produced by spleen, mediastinal, and cervica l lymph node cells, To investigate the role of IFN-gamma in control of the virus infection, mice lacking the cellular receptor for IFN-gamma (IFN-gamma R-/- mice) were infected with murine gammaherpesvirus 68 ( MHV68). IFN-gamma R-/- mice showed no difference from wild-type mice i n the titers of infectious virus in the lungs or in the rate of cleara nce of the lung infection, In the spleen, however, clear differences w ere observed. By 14 days postinfection, spleens from IFN-gamma R-/- mi ce were pale, shrunken, and fibrous, Histological examination showed t hat there was an early (day 10) infiltration of granulocytes followed by widespread destruction of splenic architecture (days 14 to 17). A m arked decrease in the number of splenic B cells and CD4(+) and CD8(+) T cells occurred, These changes were accompanied by a 10- to 100-fold greater load of latently infected cells in IFN-gamma R-/- mice than in wild-type mice at 14 to 17 days postinfection, but this was reduced t o the levels found in wild-type mice by 21 days postinfection. Treatme nt of the mice,vith the antiviral drug 2'-deoxyl-5-ethyl-beta-4'-thiou ridine from 6 days postinfection did not prevent the occurrence of the se changes, The changes were, however, completely reversed by depletio n of CD8(+) T cells prior to and during the primary infection, Depleti on of CD4(+) T cells also reversed the major pathological and virologi cal changes, although in this case there was evidence of some histolog ical changes, Thus, the lack of IFN-gamma receptor had profound conseq uences in spleens of MHV68-infected mice, The possible mechanisms invo lved in these changes are discussed.