CD40 LIGAND-MEDIATED INTERACTIONS ARE INVOLVED IN THE GENERATION OF MEMORY CD8(-LYMPHOCYTES (CTL) BUT ARE NOT REQUIRED FOR THE MAINTENANCE OF CTL MEMORY FOLLOWING VIRUS-INFECTION() CYTOTOXIC T)

CD8(+) cytotoxic T lymphocytes (CTL) play a key role in the control of many virus infections, and the need for vaccines to elicit strong CD8 (+) T-cell responses in order to provide optimal protection in such in fections is increasingly apparent. However, the mechanisms involved in the induction and maintenance of CD8+ CTL memory are currently poorly understood. In this study,we investigated the involvement of CD40 lig and (CD40L)-mediated interactions in these processes by analyzing the memory CTL response of CD40L-deficient mice following infection with l ymphocytic choriomeningitis virus (LCMV). The maintenance of memory CD 8+ CTL precursors (CTLp) at stable frequencies over time was not impai red in CD40L deficient mice. By contrast, the initial generation of me mory CTLp was affected. CD CD40L-deficient mice produced lower levels of CD8(+) CTLp during the primary immune response to LCMV than did wil d-type controls, despite the fact that the LCMV-specific effector CTL response of CD40C-deficient mice was indistinguishable from that of co ntrol animals. The differentiation of naive CD8(+) T cells into effect or and memory CTL thus involves pathways that can be discriminated fro m each other by their requirement for CD40L-mediated interactions. Exp ression of CD40L by CTLp themselves was not an essential step during t heir expansion and differentiation from naive CD8+ cells into memory C TLp; instead, the reduction in memory CTLp generation in CD40L-deficie nt mice was likely a consequence of defects in the CD4(+) T-cell respo nse mounted by these animals. These results thus suggest a previously unappreciated role for CD40L in the generation of CD8(+) memory CTLp, the probable nature of which is discussed.