Prognostic value of phenotypic alterations in blood lymphocyte subsets in a murine retrovirus-induced immunodeficiency syndrome (MAIDS)

Abstract

SUMMARY: Mice infected with the Duplan strain of murine leukaemia virus (Dup MuLV), a retrovirus, develop a syndrome sharing several features with AIDS, including lymphadenopathy and profound immunodeficiency. We measured the changes in peripheral blood lymphocyte populations and evaluated their predictive value for the outcome of disease in C57B1/6 mice. Animals were inoculated with Dup MuLV (SCI /Dup MuLV confluent fibroblast supernatant or spleen extract from an infected mouse). Peripheral blood lymphocyte subsets were sequentially monitored for 73 days using flow cytometric analysis and MoAbs directly conjugated to fluorochromes. A striking fall in the Thy 1.2 cell count occurred in diseased animals, mostly affecting the CD8+ cell compartment. At the same time, the percentage of Ly5+ cells was increased. Mice were killed at day 73 and spleen and lymph node lymphocytes were analysed. Phenotypic lymphocyte modifications in peripheral blood were closely related to those in the spleen or lymph nodes. Analysis of Ly6c antigen expression on CD4+ and CD8+ cells showed a selective expansion of the CD8+ Ly6c+ subset, which may reflect a state of immune activation. Our results suggest that phenotypic alterations of peripheral blood lymphocytes are a good marker of disease progression in this model and could be a useful criterion to evaluate antiretroviral therapy.