Recent developments in CD8+ T-lymphocyte memory research.

Abstract

Appropriately activated CD8+ T cells differentiate into cytotoxic effectors capable of eliminating cancer cells and virally infected cells. Successful generation and maintenance of effective CD8+ T-cell memory, through either natural infection or through vaccination, establishes long-term protection against various pathogenic agents and, therefore, contributes significantly to our health. This report is a review of recent advances in CD8+ T-cell memory research. The pool of memory CD8+ T cells is maintained through a mechanism of rapid turnover that is antigen-independent, class I major histocompatibility complex (MHC I) antigen-dependent, and, potentially, IL-15-dependent. Memory CD8+ T cells, in marked contrast to naive CD8+ T cells, constitutively express cytotoxic effector function in the absence of antigen stimulation. Furthermore, the vast majority of activated CD8+ T cells in mice infected with lymphocytic choriomeningitis virus are antigen-specific, prompting revision of the commonly held view that many antigen-nonspecific CD8+ T cells are activated in response to viral infection. These newly published results not only provide exciting insights into the inner workings of CD8+ memory maintenance, but they also establish a sound foundation for future investigation. As more detailed molecular and cellular mechanisms of the regulation of memory CD8+ T-cell survival emerge, the most exciting challenge will be to apply this understanding toward the rational design of vaccines and immunotherapies. These potentials are even more relevant in view of the critical nature of CD8+ T cells in combating viral infection and cancer, and the relative paucity of effective drugs against these diseases.