CD40L-DEFICIENT MICE SHOW DEFICITS IN ANTIVIRAL IMMUNITY AND HAVE AN IMPAIRED MEMORY CD8(+) CTL RESPONSE

The ligand for CD40 (CD40L) is expressed on the surface of activated C D4t(+) T cells and its role in T-B cell collaborations and thymus-depe ndent humoral immunity is well established. Recently, by generating CD 40L-knockout mice, ave have confirmed its previously described role in humoral immunity and defined another important function of this molec ule in the in vivo clonal expansion of antigen-specific CD4(+) T cells . Here, we investigated the potential in vivo role of CD40L in antivir al immunity by examining the immune response mounted by CD40L-deficien t mice following infection with lymphocytic choriomeningitis virus (LC MV), Pichinde virus, or vesicular stomatitis virus. Humoral immune res ponses of CD40L-deficient mice to these viruses were severely compromi sed, although moderate titres of antiviral IgM and some IgG2a were pro duced by virus-infected CD40L-deficient mice by a CD4(+) T cell-indepe ndent mechanism. By contrast, CD40L-deficient mice made strong primary CTL responses to all three viruses. Interestingly however, although m emory CTL activity was detectable in CD40L-deficient mice two months a fter infection with LCMV, the memory CTL response was much less effici ent than in wild-type mice. Together, the results show that CD40-CD40L interactions are required for strong antiviral humoral immune respons es, and reveal a novel role for CD40L in the establishment and/or main tenance of CD8(+) CTL memory.