CD40 LIGAND IS PIVOTAL TO EFFICIENT CONTROL OF VIRUS-REPLICATION IN MICE INFECTED WITH LYMPHOCYTIC CHORIOMENINGITIS VIRUS

CD40 ligand (CD40L) is an important molecule that is known to be invol ved in T-B collaboration and certain aspects of cell-mediated immunity . However, its role in antiviral immunity has not been clearly defined as of yet. Therefore, mice with a targeted defect in the gene encodin g this molecule were infected with one of two strains of lymphocytic c horiomeningitis virus differing markedly in their capacity to spread i n the host. Infection with lymphocytic choriomeningitis virus is initi ally controlled primarily by CD8(+) effector cells, whereas long-term immune surveillance also depends upon CD4(+) cells and B cells. Our re sults reveal that the primary activation, clonal expansion, and differ entiation of CD8(+) T cells does not require expression of CD40L. Howe ver, lack of expression results in rapid impairment of CTL responsiven ess and failure to permanently control virus replication. This happens not only in mice infected with the rapidly spreading virus strain but also at a late stage in mice infected with the strain of more limited potential for spreading. In the latter mice, virus replication is ini tially controlled very efficiently, but high levels of virus can be de tected in the blood and internal organs similar to 6 mo after virus in oculation. Since the impairment of immune function seems to be more pr onounced in CD40L-deficient mice than in mice lacking either CD4(+) ce lls or B cells, these results indicate that CD40L is pivotal to sustai n efficient antiviral immune surveillance, including CD8(+) T cells, a nd suggest that CD40L is critically involved in cellular interactions in addition to T-B cooperation.