LONG-LIVED CYTOTOXIC T-LYMPHOCYTE MEMORY IN MUCOSAL TISSUES AFTER MUCOSAL BUT NOT SYSTEMIC IMMUNIZATION

The induction and maintenance of long-term CTL memory at mucosal surfa ces may be a critical component of protection against mucosal pathogen s and is one goal towards development of effective mucosal vaccines. I n these studies we have functionally evaluated short and longterm CTL memory in systemic and respiratory or genital-associated lymphoid tiss ues following mucosal or systemic routes of immunization. Our results indicate that shortly after immunizing mice with a recombinant adenovi rus vector expressing glycoprotein B (gB) of herpes simplex virus (Adg B8), gB-specific CTL memory responses were observed in systemic and mu cosal immune compartments regardless of the route of inoculation. In c ontrast, several months after immunization, anamnestic CTL responses c ompartmentalized exclusively to mucosal or systemic lymphoid tissues a fter mucosal or systemic immunization, respectively. Furthermore, the compartmentalized CTL memory responses in mucosal tissues were functio nally observed for longer than 1.5 yr after intranasal immunization, a nd CTL precursor frequencies one year after immunization were comparab le to those seen shortly after immunization. Therefore, to our knowled ge, this is the first functional demonstration that the maintenance of anti-viral memory CTL in mucosal tissues is dependent on the route of immunization and the time of assessment. These results have important implications for our understanding of the development, maintenance, a nd compartmentalization of functional T cell memory and the developmen t and evaluation of vaccines for mucosal pathogens, such as HSV and HI V.