Granzyme B production distinguishes recently activated CD8+ memory cells from resting memory cells

For immune diagnostic purposes it would be critical to be able to distinguish between ongoing immune processes, such as active infections, and long-term immune memory, for example imprinted by infections that have been cleared a long time ago or by vaccinations. We tested the hypothesis that the secretion of granzyme B, as detected in ex vivo ELISPOT assays, permits this distinction. We studied EBV-, flu- and CMV-specific CD8+ cells in healthy individuals, Vaccinia virus-reactive CD8+ cells in the course of vaccination, and HIV-specific CD8+ cells in HIV-infected individuals. Antigen-specific ex vivo GzB production was detected only transiently after Vaccinia immunization, and in HIV-infected individuals. Our data suggest that ex vivo ELISPOT measurements of granzyme B permit the identification of actively ongoing CD8+ cell responses—a notion that is pertinent to the immune diagnostic of infections, transplantation, allergies, autoimmune diseases, tumors and vaccine development.